WO2025245302A1

WO2025245302A1 - Methods, kits and systems for determining er activity of cancer and methods for treating cancer based on same

Info

Publication number: WO2025245302A1
Application number: PCT/US2025/030476
Authority: WO
Inventors: Matthew EATON; Anthony D’IPPOLITO; Jonathan BEAGAN; Corrie PAINTER; Rehan VERJEE
Original assignee: Precede Biosciences Inc
Current assignee: Precede Biosciences Inc
Priority date: 2024-05-22
Filing date: 2025-05-21
Publication date: 2025-11-27
Anticipated expiration: 2026-11-22

Abstract

The present disclosure includes, among other things, methods, kits, and systems for determining ER activity of cancer, e.g., a breast cancer. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation to measure ER activity of a cancer. In some embodiments, differential modifications and/or differential accessibility are detected and quantified at one or more genomic loci of a biological sample, e.g., in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject with cancer. In various embodiments a determined ER activity is useful, e.g., in selecting treatment for and/or treating a cancer, e.g., a breast cancer.

Description

Attorney Docket No: 2014191-0041 METHODS, KITS AND SYSTEMS FOR DETERMINING ER ACTIVITY OF CANCER AND METHODS FOR TREATING CANCER BASED ON SAME BACKGROUND [0001] It has long been recognized that some human breast cancers are hormone dependent. Estrogen regulates the differentiation and proliferation of breast epithelial cells and interacts with the estrogen receptor (ER) in the nucleus. Prolonged exposure of estrogen is an important risk factor for cancer. Progesterone receptor (PR) expression in normal breast epithelium is regulated by ER (Jensen, Cancer (1980) 46:2759-2761). Presence of ER, PR, and human epidermal growth factor receptor-2 (HER2) status in invasive breast carcinoma is now routinely estimated as these markers are considered to be important prognostic factors. ER and PR status has been used for many years to determine a patient’s suitability for treatment with endocrine therapy (e.g., tamoxifen). [0002] To determine if a cancer is ER-positive, medical practitioners currently order testing that is conducted on a tissue sample using immunohistochemistry (IHC). Samples are reviewed by a pathologist and typically reported as (a) the word positive or negative, (b) a percentage that tells you how many cells out of 100 stained positive for hormone receptors, i.e., a number between 0% (none have receptors) and 100% (all have receptors), and/or (c) an Allred score between 0 and 8. The Allred scoring system looks at what percentage of cells test positive for hormone receptors, along with how well the receptors show up after staining, called intensity (Allred et al., Breast Cancer Res (2004) 6:240-245). This information is then combined to score the sample on a scale from 0 to 8 where, the higher the score, the more receptors were found and the easier they were to see in the sample. [0003] ER-positive cancers can be treated with ER-targeted agents that lower estrogen levels or block estrogen receptors. Conversely, treatment with ER-targeted agents is not helpful for ER-negative cancers. These cancers may instead be treated with one or more of surgery and/or radiation, HER2-targeted therapy (if HER2-positive), chemotherapy and immunotherapy. [0004] Clinical methods for measuring ER activity currently do not exist; instead, when selecting therapies, clinicians rely on ER expression status determined using a tissue sample, and assume that any cancer that expresses ER above a certain threshold level is potentially Attorney Docket No: 2014191-0041 susceptible to treatment with an ER-targeted agent. In some instances, ER status can be insufficient for best informing treatment decisions (e.g., in cases where ER+ cancers become resistant to ER-targeting agents despite being ER+). Moreover, methods that use a tissue sample are invasive and focus only on a small region at a single tumor site at a given time and therefore do not accurately capture tumor heterogeneity or receptor evolution and therefore only partially characterize the relevant patient population. [0005] There remains a need in the art for more comprehensive and precise diagnostic methods for measuring ER activity, including methods that are independent of IHC testing. Improved diagnostic methods would also better support future clinical trials that seek to identify subpopulations of patients that respond to ER-targeted agents. Improved assays for quantifying ER activity would also lead to improved methods for screening compounds for potentially use in treating ER-positive cancers (e.g., screening for compounds that can bind to and/or increase degradation of ER). Improved assays for determining ER pathway activity would also expand our understanding of the underlying biology of ER-positive cancer and help identify new treatments. SUMMARY [0006] The present disclosure is based, at least in part, on the demonstration that ER activity in a cancer can be determined by detecting and quantifying the histone modifications at one or more genomic loci in cell-free DNA (cfDNA) from a liquid biopsy sample, e.g., a plasma sample obtained or derived from a subject. The present disclosure also encompasses methods where chromatin accessibility, DNA methylation, and/or binding of one or more transcription factors are detected at one or more genomic loci instead of (or in addition to) histone modifications. The present disclosure is also based, at least in part, on the demonstration that genomic loci that are differentially modified based on different types of histone modifications (e.g., histone methylation marks such as H3K4me3 and histone acetylation marks such as H3K27ac) can be combined into an assay for quantifying ER pathway activity in a cancer. These new assays provide minimally invasive ways of determining ER activity that are more accurate, objective, and comprehensive than current tissue-based approaches. No liquid biopsy platform to date has been able to provide actionable resolution on a transcriptionally regulated Attorney Docket No: 2014191-0041 phenotype relevant for therapy such as ER activity. [0007] As discussed elsewhere in the present disclosure, blood-based assays for measuring ER activity would provide significant advantages as compared to current clinical protocols, which rely on tissue samples and ER-expression status and/or ESR1 mutations. Methods that rely on a tissue sample are invasive and focus only on a small region at a single tumor site at a given time and therefore do not accurately capture tumor heterogeneity or receptor evolution and only partially characterize the relevant patient population. In addition, efficacy of ER-targeted agents (e.g., endocrine therapies) depend on the transcriptional addiction of cancer cells to estrogen receptor signaling, for which there is no current clinical test. ER status and ESR1 mutations are insufficient proxies for ER transcriptional dependency. Methods that detect ER activity in a cell, rather than simply ER expression status or ESR1 mutation status would therefore provide significant advantages, including, e.g., being better able to predict patient responsiveness to treatment with ER-targeted therapies and/or better inform therapy selection. [0008] The present disclosure includes, among other things, technologies for determining ER activity and for the detection, monitoring, and/or treatment of cancer (including, e.g., breast, ovarian, or endometrial cancer) based on ER activity. In various embodiments, the present disclosure relates to the measurement of histone modifications in a sample obtained or derived from a subject to detect and/or treat cancer (including, e.g., breast, ovarian, or endometrial cancer) based on ER activity. The present disclosure includes, among other things, histone modification measurements in cell-free DNA (cfDNA) that are characteristic of cancer, and which in various embodiments are useful, e.g., for detecting, monitoring, selecting treatment for, and/or treating cancer (including, e.g., breast, ovarian, or endometrial cancer) based on ER activity. In some embodiments, histone modification measurements in cfDNA can be used to detect or determine resistance of a cancer (e.g., breast, ovarian, or endometrial cancer) to a therapy or transformation of a cancer from one subtype to another. In various embodiments, the present disclosure includes exemplary genomic loci that comprise differential epigenomic modifications depending on ER activity in a cancer (e.g., breast, ovarian, or endometrial cancer). In various embodiments, genomic loci differentially modified in cfDNA are or include one or more enhancers. In various embodiments, genomic loci differentially modified in cfDNA are or Attorney Docket No: 2014191-0041 include one or more promoters. [0009] Among other things, the present disclosure also provides certain insights for measuring and/or adjusting for mechanisms of resistance to ER-targeted agents. These insights include selecting genomic loci that exhibit increased promoter or enhancer signal in the presence of estrogen and that also meet certain criteria, including proximity to an ER binding site, proximity to a gene that is repressed in cancers that have acquired resistance to an ER-targeted agent, and/or selecting genomic loci that are not in close proximity to a locus associated with resistance to an ER-targeted agent (including, e.g., FOXA1 binding sites associated with tamoxifen resistance). Additional insights provided by the present disclosure include, adjusting for (i) enhancer or promoter signal at one or more genomic loci that exhibit increased enhancer or promoter signal when a cell is deprived of estrogen, and/or (ii) enhancer or promoter signal at one or more genomic loci associated with a mechanism for resistance to an ER-targeted agent (including, e.g., one or more genomic loci associated with FOXA1-mediated resistance to tamoxifen). [0010] As used herein, a cell line that has been "deprived" of estrogen refers to a cell line that was first cultured in a media that included estrogen (e.g., exogenous estrogen and/or serum comprising estrogen) and then transferred to a media that lacked estrogen (e.g., media that lacks exogenous estrogen and/or culture media comprising sera in which estrogen has been removed (e.g., via charcoal stripping)). [0011] In various embodiments, a genomic locus is differentially modified if it is characterized by increased or decreased histone modification as compared to a reference (e.g., a sample from an ER-negative or healthy subject, a cell line treated with exogenous estrogen, a cell line cultivated in media that lacks estrogen, or a cell line deprived of estrogen). Increased or decreased histone modification can be or include, e.g., increased or decreased histone methylation (hypermethylation or hypomethylation, respectively) of one or more particular methylation marks, or a combination thereof; increased or decreased pan-methylation; increased or decreased histone acetylation (hyperacetylation or hypoacetylation, respectively) of one or more particular acetylation marks, or a combination thereof; and/or increased or decreased pan- acetylation (e.g., pan-H3 acetylation). In various embodiments, histone methylation can be or include histone methylation marks selected from H3K4me1, H3K4me2, H3K4me3, or a combination thereof. In various embodiments, histone methylation can be or include H3K4me3. Attorney Docket No: 2014191-0041 In various embodiments, histone acetylation can be or include histone acetylation marks selected from H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac, or a combination thereof. In various embodiments, histone acetylation can be or include H3K27ac. [0012] In various embodiments, the present disclosure relates to the measurement of DNA methylation in a sample obtained or derived from a subject to detect and/or treat cancer (including, e.g., breast, ovarian, or endometrial cancer) based on ER activity. In some embodiments, DNA methylation measurements in cfDNA can be used to detect or determine resistance of a cancer (e.g., breast, ovarian, or endometrial cancer) to a therapy or transformation of a cancer from one subtype to another. In various embodiments, a genomic locus is differentially modified if it is characterized by increased or decreased DNA methylation as compared to a reference (e.g., a sample from an ER-negative or healthy subject, a cell line treated with exogenous estrogen, a cell line cultivated in media that lacks estrogen, or a cell line deprived of estrogen). In various embodiments, genomic loci differentially modified in cfDNA are or include one or more enhancers. In various embodiments, genomic loci differentially modified in cfDNA are or include one or more promoters. [0013] The present disclosure further relates, in various embodiments, to the measurement of chromatin accessibility in cell-free DNA (cfDNA) to determine ER activity. The present disclosure includes, among other things, chromatin accessibility measurements in cfDNA that are associated with ER activity in cancers, which in various embodiments are useful, e.g., in detecting, monitoring, selecting treatment for, and/or treating an ER-positive cancer. In some embodiments, chromatin accessibility measurements in cfDNA can be used to detect or determine resistance of a cancer (e.g., breast, ovarian, or endometrial cancer) to a therapy or transformation of a cancer from one subtype to another. In various embodiments, the present disclosure includes genomic loci that are differentially accessible based on ER activity. In various embodiments, genomic loci differentially accessible in cfDNA are or include one or more enhancers. In various embodiments, genomic loci differentially accessible in cfDNA are or include one or more promoters. [0014] In various embodiments, without wishing to be bound by any particular scientific theory, histone methylation (e.g., H3K4me3) corresponds and/or is correlated with chromatin accessibility. In various embodiments, without wishing to be bound by any particular scientific theory, histone acetylation (e.g., H3K27ac) corresponds and/or is correlated with chromatin Attorney Docket No: 2014191-0041 accessibility. In various embodiments, without wishing to be bound by any particular scientific theory, DNA methylation corresponds and/or is correlated with chromatin accessibility. [0015] In various embodiments, a genomic locus is differentially accessible if it is characterized by increased or decreased chromatin accessibility as compared to a reference (e.g., a sample from an ER-negative or healthy subject, a cell line treated with exogenous estrogen, a cell line cultivated in media that lacks estrogen, or a cell line deprived of estrogen). Increased or decreased histone modification can be or include, e.g., increased or decreased accessibility as determined by various chromatin accessibility assays known in the art. [0016] The present disclosure further relates, in various embodiments, to the measurement of transcription factor binding in cell-free DNA (cfDNA) to determine ER activity. The present disclosure includes, among other things, transcription factor binding measurements in cfDNA that are characteristic of ER activity in cancers, which in various embodiments are useful, e.g., in detecting, monitoring, selecting treatment for, and/or treating an ER-positive cancer. In some embodiments, transcription factor binding measurements in cfDNA can be used to detect or determine resistance of a cancer (e.g., breast, ovarian, or endometrial cancer) to a therapy or transformation of a cancer from one subtype to another. In various embodiments, the present disclosure includes genomic loci that are differentially bound by transcription factors depending on ER activity in a cancer. In various embodiments, genomic loci that are differentially bound by transcription factors in cfDNA are or include one or more enhancers. In various embodiments, genomic loci that are differentially bound by transcription factors in cfDNA are or include one or more promoters. [0017] In various embodiments, without wishing to be bound by any particular scientific theory, histone methylation (e.g., H3K4me3) corresponds and/or is correlated with transcription factor binding. In various embodiments, without wishing to be bound by any particular scientific theory, histone acetylation (e.g., H3K27ac) corresponds and/or is correlated with transcription factor binding. In various embodiments, without wishing to be bound by any particular scientific theory, DNA methylation corresponds and/or is correlated with transcription factor binding. [0018] In various embodiments, a genomic locus is differentially bound by transcription factors if it is characterized by increased or decreased transcription factor binding as compared to a reference (e.g., a sample from an ER-negative or healthy subject, a cell line treated with exogenous estrogen, a cell line cultivated in media that lacks estrogen, or a cell line deprived of Attorney Docket No: 2014191-0041 estrogen). Increased or decreased transcription factor binding can be or include, e.g., increased or decreased transcription factor binding as determined by various transcription factor binding assays known in the art. [0019] In some embodiments, methods provided herein can result in improved therapeutic outcomes in a subject with an ER+ cancer. In some cancers there is a disconnect between ER expression status and ER activity, such that, even though a cancer is ER+, ER pathway activity may be low, and a subject may show a poor or no response to treatment with an ER-targeting agent despite having an ER+ cancer. Thus, methods that can determine ER activity (e.g., as described herein), can, in some embodiments, provide for improved therapeutic outcomes in subjects having an ER+ cancer as compared to methods that rely on ER expression status alone. Methods comprising determining ER activity (e.g., as described herein) are also useful for detecting when a disease becomes resistant to ER-targeting agents (rather than, e.g., waiting for a subject’s cancer to progress) and/or when alternative, non-ER targeting agents would be preferred. [0020] In some embodiments, provided herein is a method of measuring estrogen receptor (ER) pathway activity of a cancer in a subject, the method comprising: quantifying, at one or more genomic loci in a biological sample, optionally in cell-free DNA (cfDNA) from a liquid biopsy sample, obtained or derived from the subject: (i) one or more histone modifications, (ii) chromatin accessibility, (iii) binding of one or more transcription factors, and/or (iv) DNA methylation. [0021] In some embodiments, one or more histone modifications are quantified using a histone modification assay that measures one or more of H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac, H3K4me1, H3K4me2, H3K4me3, and pan-acetylation. [0022] In some embodiments, a histone modification assay detects H3K4me3 modifications. [0023] In some embodiments, a histone modification assay detects H3K27ac modifications. [0024] In some embodiments, a histone modification assay is selected from ChIP-seq (Chromatin ImmunoPrecipitation sequencing), CUT&RUN (Cleavage Under Targets and Attorney Docket No: 2014191-0041 Release Using Nuclease) sequencing, and CUT&Tag (Cleavage Under Targets and Tagmentation) sequencing. [0025] In some embodiments, a chromatin accessibility is quantified using a chromatin accessibility assay selected from ATAC-seq (Assay of Transpose Accessible Chromatin sequencing), NOMe-seq (Nucleosome Occupancy and Methylome sequencing), FAIRE-seq (Formaldehyde-Assisted Isolation of Regulatory Elements sequencing), MNase-seq (Micrococcal Nuclease digestion with sequencing), a DNase hypersensitivity assay, or a fragmentomics assay. [0026] In some embodiments, binding of one or more transcription factors is quantified using a transcription factor binding assay that detects binding of one or more of p300, mediator complex, cohesion complex, RNA pol II, FOXA1, ESR1, PR, MYC, EN1, FOXM1, KLF4, AP- 2, RARa, RUNX1, or any combination thereof. [0027] In some embodiments, a transcription factor binding assay is selected from ChIP- seq (Chromatin ImmunoPrecipitation sequencing), CUT&RUN (Cleavage Under Targets and Release Using Nuclease) sequencing, and CUT&Tag (Cleavage Under Targets and Tagmentation) sequencing. [0028] In some embodiments, DNA methylation is quantified using Bisulfite sequencing (BS-Seq), Whole Genome Bisulfite Sequencing (WGBS), Methylated DNA ImmunoPrecipitation sequencing (MeDIP-seq), or Methyl-CpG-Binding Domain sequencing (MBD-seq). [0029] In some embodiments, a method comprises quantifying two or more of the following, each at one or more genomic loci in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject: (i) one or more histone modifications, (ii) chromatin accessibility, (iii) transcription factor binding, and/or (iv) DNA methylation. [0030] In some embodiments, a method comprises quantifying two or more histone modifications. [0031] In some embodiments, a method comprises quantifying H3K4me3 and H3K27ac Attorney Docket No: 2014191-0041 modifications. [0032] In some embodiments, one or more genomic loci described herein are characterized in that they exhibit increased signal in: (i) an ER+ cancer (e.g., one or more samples obtained from one or more subjects having an ER+ cancer) as compared to an ER- cancer (e.g., one or more samples obtained from one or more subjects having an ER+ cancer); (ii) an mESR1 cancer (e.g., one or more samples obtained from one or more subjects having an mESR1 cancer) as compared to a cancer without an mESR1 mutation (e.g., one or more samples obtained from one or more subjects not having an mESR1 cancer); and/or (iii) one or more ER+ cancer cell lines incubated with exogenous estrogen as compared to one or more ER+ cancer cell lines not incubated with exogenous estrogen and/or one or more ER- cancer cell lines. [0033] In some embodiments, a liquid biopsy sample is a plasma sample, serum sample, or urine sample. [0034] In some embodiments, a comprises quantifying: (i) one or more histone modifications at one or more regulatory regions (e.g., promoter or enhancer regions) associated with one or more genes listed in Tables 1-8, (ii) chromatin accessibility at one or more of the genes listed in Tables 1-8, (iii) binding of one or more transcription factors associated with activation and/or repression of the estrogen receptor signaling pathway (e.g., transcription factors associated with promoting or repressing expression of one or more of the genes listed in Tables 1-8), and/or (iv) DNA methylation of one or more of the genes listed in Tables 1-8. [0035] In some embodiments, a method comprises quantifying promoter signal and/or enhancer signal associated with one or more of the genes listed in Tables 1-8 (e.g., quantifying promoter signal at one or more of the promoter loci listed in Table 1, 3, or 4 and/or quantifying enhancer signal at one or more of the enhancer loci listed in Table 2, 5, 6, 9 or 10). In some embodiments, a method comprises quantifying promoter signal at a promoter of one or more genes induced by ER pathway activation (e.g., quantifying promoter signal at one or more of the induced promoter loci listed in Table 1 or 3). [0036] In some embodiments, a method comprises quantifying enhancer signal at one or Attorney Docket No: 2014191-0041 more enhancer regions associated with one or more genes induced by ER pathway activation (e.g., quantifying enhancer signal at one or more of the induced enhancer loci listed in Table 2, 5, or 9). [0037] In some embodiments, one or more genes induced by ER pathway activation comprise 5, 6, or 7 of the induced genes listed in any one of Tables 1-8 (e.g., AMZ1, CELSR2, FKBP4, GREB1, OLFM1, SLC9A3R1, and/or TFF1). [0038] In some embodiments, one or more genes induced by ER pathway activation comprise 5, 6, 7, 8, 9, or 10 of the induced genes listed in any one of Tables 1-8 (e.g., AMZ1, AREG, CELSR2, FKBP4, FMN1, GREB1, OLFM1, RBM24, SLC9A3R1, and/or TFF1). [0039] In some embodiments, one or more genes induced by ER pathway activation comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the induced genes listed in any one of Tables 1-8 (e.g., AMZ1, AREG, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, and/or ZNF703). [0040] In some embodiments, the present disclosure provides a method that comprises: (i) summing promoter signal at two or more of the induced promoter loci listed in Table 1, 3, or 4, (ii) summing enhancer signal at two or more of the induced enhancer loci listed in Table 2, 5, 6, 9, or 10; (iii) summing promoter signal at two or more of the repressed promoter loci listed in Table 1, and/or (iv) summing enhancer signal at two or more repressed enhancer loci listed in Table 2. [0041] In some embodiments, promoter signal comprises H3K4me3 signal, and/or enhancer signal comprises H3K27ac signal. [0042] In some embodiments, the present disclosure provides a method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining a promoter score for the sample, wherein the promoter score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) promoter Attorney Docket No: 2014191-0041 signal at one or more of the induced promoter loci listed in Table 1, and (ii) dividing the result of (i) by the sum of promoter signal at one or more of the repressed promoter loci listed in Table 1. [0043] In some embodiments, the present disclosure describes a method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining a promoter score for the sample, wherein the promoter score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the induced promoter loci listed in Table 1, (ii) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the repressed promoter loci listed in Table 1, (ii) dividing the result of (i) by the result of (ii). [0044] As used herein, two measurements (e.g., measurements of one or more epigenetic modifications at two or more genomic loci) can be combined. As used herein, “combined” or “combining” and the like using an appropriate means that reflects each of the two measurements (e.g., epigenetic modification levels at each of two or more genomic loci). Exemplary methods for combining two or more measurements (e.g., measurements of epigenetic modifications at two or more genomic loci) include summing, averaging, geometric mean averaging, etc. In some embodiments, sequence reads at one or more enhancer loci can be processed before combining, including, e.g., correcting for background signal and/or for sequencing depth. [0045] In some embodiments, the present disclosure provides a method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining an enhancer score for the sample, wherein the enhancer score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) Attorney Docket No: 2014191-0041 enhancer signal at one or more of the induced enhancer loci listed in Table 2, and (ii) dividing the result of (i) by a combined measure of (e.g., sum, average, geometric mean average) enhancer signal at one or more of the repressed enhancer loci listed in Table 2. [0046] In some embodiments, the present disclosure provides a method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining an enhancer score for the sample, wherein the enhancer score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the induced enhancer loci listed in Table 2, (ii) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the repressed enhancer loci listed in Table 2, and (ii) dividing the result of (i) by the result of (ii). [0047] In some embodiments, the present disclosure provides a method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining an ER-induced score for the sample, wherein the ER-induced score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the induced promoter loci listed in Table 1, (ii) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the induced enhancer loci listed in Table 2, and (iii) adding the result of (i) and (ii). [0048] In some embodiments, a method of measuring ER pathway activity of a cancer in a subject, comprises: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a Attorney Docket No: 2014191-0041 liquid biopsy sample, from the subject; determining an ER pathway activity score for the sample, wherein the ER pathway activity score is determined by a method comprising determining a promoter score and an enhancer score, wherein the promoter score is determined by a method comprising: (i) combining (e.g., summing, averaging, and/or geometric mean averaging) promoter signal at one or more of the induced promoter loci listed in Table 1, and (ii) dividing the result of (i) by the sum of promoter signal at one or more of the repressed promoter loci listed in Table 1, and wherein the enhancer score is determined by a method comprising: (iii) summing enhancer signal at one or more of the induced enhancer loci listed in Table 2, and (iv) dividing the result of (iii) by the sum of enhancer signal at one or more of the repressed enhancer loci listed in Table 2, and wherein the ER pathway activity score is determined by adding the promoter score and the enhancer score. [0049] In some embodiments, a method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining an ER pathway activity score for the sample, wherein the ER pathway activity score is determined by a method comprising combining (e.g., summing) a promoter score and an enhancer score, wherein: (a) the promoter score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the induced promoter loci listed in Table 1, (ii) combining (e.g., summing, averaging, or geometric mean averaging) promoter Attorney Docket No: 2014191-0041 signal at one or more of the repressed promoter loci listed in Table 1, (ii) dividing the result of (a)(i) by the result of (a)(ii); and (b) the enhancer score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the induced enhancer loci listed in Table 2, (ii) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the repressed enhancer loci listed in Table 2, and (ii) dividing the result of (b)(i) by the result of (b)(ii). [0050] In some embodiments, a promoter score and an enhancer score are scaled prior to being added. In some embodiments, a promoter score and an enhancer score are scaled prior to combining such that the maximum and minimum enhancer signal scores have the same value as the maximum and minimum promoter scores (e.g., to provide values between 0 and 1). [0051] In some embodiments, an ER promoter score, ER enhancer score, and/or an ER activity score is corrected for ctDNA%. [0052] In some embodiments, one or more induced promoter loci comprise 5, 6, or 7 of the promoter regions of induced genes listed in Table 1 (including, e.g., AMZ1, CELSR2, FKBP4, GREB1, OLFM1, SLC9A3R1, and/or TFF1). [0053] In some embodiments, one or more induced promoter loci comprise 5, 6, 7, 8, 9, or 10 of the promoter regions of induced genes listed in Table 1 (e.g., AMZ1, AREG, CELSR2, FKBP4, FMN1, GREB1, OLFM1, RBM24, SLC9A3R1, and/or TFF1). [0054] In some embodiments, one or more induced promoter loci comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the promoter regions of induced genes listed in Table 1 (e.g., AMZ1, AREG, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, and/or ZNF703). [0055] In some embodiments, one or more induced enhancer loci comprise one or more enhancer regions associated with 5, 6, or 7 of the induced genes listed in Table 1 (including, e.g., AMZ1, CELSR2, FKBP4, GREB1, OLFM1, SLC9A3R1, and/or TFF1). [0056] In some embodiments, one or more induced enhancer loci comprise one or more Attorney Docket No: 2014191-0041 enhancer regions associated with 5, 6, 7, 8, 9, or 10 of the promoter regions of induced genes listed in Table 1 (e.g., AMZ1, AREG, CELSR2, FKBP4, FMN1, GREB1, OLFM1, RBM24, SLC9A3R1, and/or TFF1) [0057] In some embodiments, one or more induced enhancer loci comprise one or more enhancer regions associated with 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the enhancer regions of induced genes listed in Table 1 (e.g., AMZ1, AREG, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, and/or ZNF703). [0058] In some embodiments, one or more repressed promoter loci comprise 5, 6, or 7 of the promoter regions of repressed genes listed in Table 1. [0059] In some embodiments, one or more repressed promoter loci comprise 5, 6, 7, 8, 9, or 10 of the promoter regions of repressed genes listed in Table 1. [0060] In some embodiments, one or more repressed promoter loci comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 of the promoter regions of repressed genes listed in Table 1. [0061] In some embodiments, one or more repressed promoter loci comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the promoter regions of repressed genes listed in Table 1. [0062] In some embodiments, one or more repressed enhancer loci comprise one or more enhancer regions associated with 5, 6, or 7 of the repressed genes listed in Table 1. [0063] In some embodiments, one or more repressed enhancer loci comprise one or more enhancer regions associated with 5, 6, 7, 8, 9, or 10 of the repressed genes listed in Table 1. [0064] In some embodiments, one or more repressed enhancer loci comprise one or more enhancer regions associated with 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the enhancer regions of repressed genes listed in Table 1. [0065] In some embodiments, a method comprises quantifying H3K4me3 modifications for at least 5, 10, 20, or 30 or more of the genomic promoter loci listed in Table 1. [0066] In some embodiments, promoter signal comprises H3K4me3, and/or enhancer signal comprises H3K27ac. [0067] In some embodiments, promoter signal comprises a measure of H3K4me3 modifications, and/or enhancer signal comprises a measure of H3K27ac modifications. [0068] In some embodiments, a method comprises quantifying H3K27ac modifications Attorney Docket No: 2014191-0041 for at least 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 2. [0069] In some embodiments, a method of measuring ER pathway activity of a cancer in a subject comprises: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; and measuring ER activity using a method comprising measuring levels of enhancer signal or promoter signal in the cfDNA at one or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal in one or more cell lines (e.g., ER+ breast cancer cell lines) treated with exogenous estrogen as compared to one or more cell lines (e.g., ER+ breast cancer cell lines) not treated with exogenous estrogen and/or one or more cell lines (e.g., ER+ breast cancer cell lines) deprived of estrogen. [0070] In some embodiments, one or more loci that have been shown to exhibit increased levels of promoter signal in one or more cell lines include at least 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 3. [0071] In some embodiments, one or more loci that have been shown to exhibit increased levels of enhancer signal in one or more cell lines include at least 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 5. [0072] In some embodiments, a method comprises measuring enhancer signal only at one or more genomic loci that have been shown to exhibit increased levels of enhancer signal and that are within 10,000 bp (e.g., 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 bp) of an ER binding site. [0073] In some embodiments, a method comprises measuring enhancer signal only at one or more genomic loci that have been shown to exhibit increased levels of enhancer signal and that are within 500,000 bp (e.g., within 400,000; 300,000; 200,000; 150,000; 100,000; or 50,000 bp) of a gene that is repressed in a cancer that is resistant to treatment with ER-targeted therapies. [0074] In some embodiments, a method comprises measuring enhancer signal only at one or more genomic loci that have been shown to exhibit increased levels of enhancer signal and that are not within 10,000 bp (e.g., 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 bp) of a FOXA1 binding site associated with resistance to tamoxifen. [0075] In some embodiments, one or more genomic loci that have been shown to exhibit Attorney Docket No: 2014191-0041 increased levels of enhancer signal comprise one of more genomic loci within an enhancer region of at least 1, 5, 10, 15, 20, 25, 30, 35, 40, or 50 of the genes listed in Table 7. [0076] In some embodiments, one or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal comprise at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 9. [0077] In some embodiments, a method comprises measuring enhancer signal or promoter signal at two or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal, and combining (e.g., summing, averaging (including, e.g., geometric mean averaging and/or weighted sum averaging) the enhancer signal or promoter signal measured at the two or more genomic loci. [0078] In some embodiments, a method further comprises determining enhancer signal or promoter signal at: (a) one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer (e.g., ER+ breast cancer) cell lines deprived of exogenous estrogen; and/or (b) one or more genomic loci that are in close proximity (e.g., loci within 10,000; 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 bp) to a FOXA1 binding site associated with resistance to tamoxifen. [0079] In some embodiments, a method comprises determining enhancer signal or promoter signal at: (a) one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer (e.g., ER+ breast cancer) cell lines deprived of exogenous estrogen as compared to the same cancer cell lines cultured with incubated with media comprising exogenous estrogen; and/or (b) one or more genomic loci that are in close proximity (e.g., loci within 10,000, 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 bp) to a FOXA1 binding site associated with resistance to tamoxifen. [0080] In some embodiments, a method comprises combining (e.g., summing, averaging (including, e.g., weighted sum averaging and/or geometric mean averaging) enhancer or promoter signal measured at (a) the one or more genomic loci that have been shown to exhibit increased enhancer signal or promoter signal in cancer cell lines deprived of exogenous estrogen; Attorney Docket No: 2014191-0041 and (b) the one or more genomic loci that are in close proximity to a FOXA1 binding site associated with resistance to tamoxifen. [0081] In some embodiments, a method comprises adjusting the combined enhancer signal or promoter signal measured at two or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal in cell lines incubated with media comprising exogenous estrogen as compared to cell lines not incubated with exogenous estrogen and/or deprived of exogenous estrogen for the combined enhancer and promoter signal measured at (a) the one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer cell lines deprived of exogenous estrogen; and (b) the one or more genomic loci that are in close proximity to a FOXA1 binding site associated with resistance to tamoxifen. [0082] In some embodiments, a method comprises subtracting the combined enhancer and promoter signal measured at (a) the one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer cell lines deprived of exogenous estrogen; and (b) the one or more genomic loci that are in close proximity to a FOXA1 binding site associated with resistance to tamoxifen from the combined enhancer signal or promoter signal measured at two or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal in cell lines incubated with media comprising exogenous estrogen as compared to cell lines not incubated with exogenous estrogen and/or deprived of exogenous estrogen. [0083] In some embodiments, enhancer signal and/or promoter signal in the liquid biopsy sample is measured using a method that comprises sequencing cfDNA comprising one or more histone modifications (e.g., H3K4me3 and/or H3K27ac), e.g., using cfChIP-seq. [0084] In some embodiments, sequence reads at each genomic loci are processed prior to combining with sequence reads at other genomic loci (e.g., quantile normalized and/or adjusted for background signal. [0085] In some embodiments, one or more genomic loci described herein are characterized in that they exhibit low signal in healthy patient samples, and/or are regions at which signal of one or more epigenetic modification is correlated with ctDNA% (e.g., estimated ctDNA%). [0086] In some embodiments, one or more genomic loci described herein are Attorney Docket No: 2014191-0041 characterized in that they exhibit increased signal in: (i) an ER+ cancer (e.g., one or more samples obtained from one or more subjects having an ER+ cancer) as compared to an ER- cancer (e.g., one or more samples obtained from one or more subjects having an ER+ cancer); (ii) an mESR1 cancer (e.g., one or more samples obtained from one or more subjects having an mESR1 cancer) as compared to a cancer without an mESR1 mutation (e.g., one or more samples obtained from one or more subjects not having an mESR1 cancer); and/or (iii) one or more ER+ cancer cell lines incubated with exogenous estrogen as compared to one or more ER+ cancer cell lines not incubated with exogenous estrogen and/or one or more ER- cancer cell lines; optionally wherein the signal is increased by an absolute log2(fold-change) of at least 2.0 (e.g., at least 2.5, at least 3.0, at least 3.5, or at least 4.0). [0087] In some embodiments, a liquid biopsy sample is a plasma sample, serum sample, or urine sample. [0088] In some embodiments, the present disclosure provides a method for determining whether a cancer in a subject is ER-positive or ER-negative, the method comprising: (i) obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; and (ii) measuring ER activity (e.g., determining an ER activity score using a method of any one of claims 26-44) in the biological sample, wherein the ER activity is determined by a method of any one of claims 23-59, wherein the cancer is determined to be ER-positive if the ER pathway activity score is greater than or equal to a threshold value, and the cancer is determined to be ER- negative if the ER pathway activity score is less than the threshold value. [0089] Among other things, the present disclosure describes a method of treating a subject having cancer, a method of predicting a subject having cancer’s responsiveness to an ER- targeted agent, a method of predicting a subject having cancer’s susceptibility to treatment with an ER-targeted agent, or a method of predicting a subject having cancer’s resistance to treatment with an ER-targeted agent, comprising measuring ER pathway activity using a method described Attorney Docket No: 2014191-0041 herein. [0090] In some embodiments, the present disclosure provides a method of treating a subject having a cancer, the method comprising: administering an ER-targeted agent to the subject if the cancer is determined to be ER-positive, and not administering a cancer therapy if the cancer is determined to be ER-negative, wherein the cancer is determined to be ER-positive or ER-negative using a method provided herein. [0091] In some embodiments, the present disclosure provides a method of treating cancer in a subject, the method comprising: (i) obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; (ii) determining ER activity (e.g., determining an ER activity score using a method of any one of claims 26-44) in the biological sample, wherein the ER activity is determined using a method of any one of claims 23-59; (iii) administering an ER-targeted agent to the subject if the ER activity is greater than or equal to reference value (e.g., a threshold value), and not administering an ER-targeted agent to the subject if the ER activity is less than the reference value (e.g., threshold value). [0092] In some embodiments, a reference value (e.g., threshold value) is a predetermined threshold value and/or a normalized value. [0093] In some embodiments, a reference value (e.g., threshold value) is an ER activity measurement (e.g., an ER pathway activity score) determined in a reference population. [0094] In some embodiments, a reference population comprises subjects having cancer and previously found to respond to treatment with an ER-targeted agent. [0095] In some embodiments, a reference population comprises subjects having cancer and previously found to not respond to treatment with an ER-targeted therapy, and wherein the threshold value is greater than the ER activity score determined in the reference population. [0096] In some embodiments, a reference population comprises subjects having an ER- positive cancer (e.g., as determined by IHC). [0097] In some embodiments, a reference population comprises subjects having an ER- Attorney Docket No: 2014191-0041 negative cancer (e.g., as determined by IHC) or determined to be cancer free, and wherein the reference value (e.g., threshold value) is greater than the ER activity score determined in the reference population. [0098] In some embodiments, a reference is the lower bound of the bottom quintile, the lower bound of the top quartile, the lower bound of the top tertile, the median, the lower bound of the fourth quintile, the lower bound of the top tertile, the lower bound of the quartile, or the lower bound of the top quintile of ER pathway activity values determined in a reference population (e.g., a population of breast cancer patient or a population of ER+ breast cancer patients). [0099] In some embodiments, a subject has previously been determined to have cancer. [0100] In some embodiments, a subject has previously been determined to have breast cancer, optionally wherein the cancer is ER+ breast cancer (e.g., as determined using IHC). [0101] In some embodiments, ER targeted agent is administered to the subject if ER pathway activity score is between about 0.25 and about 2.00, about 0.30 and about 2.00, about 0.35 and about 2.00, about 0.40 and about 2.00, about 0.45 and about 2.00, about 0.50 and about 2.00, about 0.55 and about 2.00, or about 0.60 and about 2.00. [0102] In some embodiments, the present disclosure provides a method of monitoring cancer (e.g., ER-positive cancer) in a subject, and optionally treating the cancer, the method comprising: measuring ER activity of the cancer using a method described herein at a first and a second time point. [0103] In some embodiments, a subject has been administered an ER-targeted agent prior to the first time point or after a first time point and before a second time point. [0104] In some embodiments, a method comprises administering an ER-targeted agent to a subject based on the change in ER activity between a first time point and a second time point, optionally wherein the type, dose and/or frequency of administration of the ER-targeted therapy is adjusted based on the change in ER activity. [0105] In some embodiments, a subject has an improved probability of responding to an ER-targeted agent if ER pathway activity decreases between a first time point and a second time point. [0106] In some embodiments, a method comprises continuing to administer an ER- Attorney Docket No: 2014191-0041 targeted agent (e.g., administering one or more additional doses of an ER-targeted therapy) if ER pathway activity increases or stays approximately the same between a first time point and a second time point. [0107] In some embodiments, if ER pathway activity decreases, a method comprises increasing the amount of ER-targeted agent administered to the subject, and/or administering a different ER-targeted agent to the subject. [0108] In some embodiments, a method comprises determining enhancer or promoter signal at: (a) one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer (e.g., ER+ breast cancer) cell lines deprived of exogenous estrogen; and/or (b) one or more genomic loci that are in close proximity (e.g., loci within 10,000; 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 bp) to a FOXA1 binding site associated with resistance to tamoxifen; and, if enhancer or promoter signal is increased at either of genomic loci (a) or (b), administering a therapy that does not comprise an ER-targeted agent, and, if enhancer or promoter signal is increased at either of genomic loci (a) or (b), continuing to administer an ER- targeted agent. [0109] In some embodiments, a method comprises combining (e.g., summing, averaging (including, e.g., weighted sum averaging and/or geometric mean averaging) enhancer or promoter signal measured at (a) one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer cell lines deprived of exogenous estrogen; and (b) one or more genomic loci that are in close proximity to a FOXA1 binding site associated with resistance to tamoxifen; and if the combined enhancer or promoter signal increases between the first time point and the second time point, ceasing administering the ER-targeted agent; and if the combined enhancer or promoter signal decreases or stays approximately the same between the first time point and the second time point, continuing to administer the ER-targeted agent. [0110] In some embodiments, a cancer is breast cancer, ovarian cancer, or endometrial Attorney Docket No: 2014191-0041 cancer. [0111] In some embodiments, a cancer is breast cancer (e.g., ER+ breast cancer). [0112] In some embodiments, the present disclosure provides a method for testing the ER-targeting activity of a compound, comprising incubating the compound with a cell line, and measuring ER activity in the cell line subsequent to incubating the compound with the cell line, wherein the ER activity is measured using a method described herein. [0113] In some embodiments, ER targeting activity is measured using a method that comprises measuring ER activity score described herein. [0114] In some embodiments, a cell line has measurable ER activity (e.g., the cell line has been incubated with a composition that increases ER signaling activity (e.g., estrogen or a derivative thereof)) prior to incubating with a compound for which ER-targeting activity is being tested. [0115] In some embodiments, a cell line is a cancer cell line, a breast cancer cell line, an ER+ cancer cell line, or an ER+ breast cancer cell line. [0116] In some embodiments, a method comprises comparing ER pathway activity measured in a cell line incubated with a compound for which ER-targeting activity is being tested to ER pathway activity measured in a cell line not incubated with the compound, wherein the ER pathway activity of each cell line has been measured using technologies described herein, and optionally wherein the cell line incubated with the compound and the cell line not incubated with the compound are the same cell line. [0117] In some embodiments, a method comprises comparing ER pathway activity measured in a cell line incubated with a compound for which ER-targeting activity is being tested to ER pathway activity measured in a cell line deprived of exogenous estrogen, optionally wherein (i) the cell line deprived of exogenous estrogen has also been incubated with the compound before and/or after estrogen deprivation and/or (ii) the two cell lines are the same cell line. [0118] In some embodiments, a cell line not incubated with a compound for which ER- targeting activity is being tested has measurable ER pathway activity, (e.g., wherein has been incubated with a composition that increases ER signaling activity (e.g., estrogen or a derivative Attorney Docket No: 2014191-0041 thereof)). [0119] In some embodiments, a cell line not incubated with a compound for which ER- targeting activity is being tested and/or a cell line deprived of exogenous estrogen is a cancer cell line, a breast cancer cell line, an ER+ cancer cell line, or an ER+ breast cancer cell line. [0120] In some embodiments, the present disclosure provides method for screening a library of compounds for ER-targeting activity, the method comprising testing the activity of each compound using a method described herein. [0121] In some embodiments, the present disclosure provides an ER-targeting agent, wherein the ER targeting agent has been identified using a method described herein. [0122] In some embodiments, the present disclosure provides a kit comprising reagents for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci, wherein the one or more genomic loci are selected from those listed in Table 1, 2, 3, 4, 5, 6, 9, or 10. [0123] In some embodiments, a kit comprises reagents for quantifying H3K4me3 for: (a) at least 5, 10, 20, 30, or 38 genomic loci listed in Table 1; (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 3; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 4; or (d) any combination of (a)-(c). [0124] In some embodiments, a kit comprises reagents for quantifying H3K27ac for: (a) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 2; (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 5; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 6; (d) at least 1, 5, 10, 20, 30, or 40 genomic loci listed in Table 9; (e) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 10; or (f) any combination of (a)-(e). [0125] In some embodiments, a kit comprises one or more antibodies for use in ChIP- seq, optionally wherein the one or more antibodies specifically bind H3K4me3- or H3K27ac- modified histones. [0126] In some embodiments, a kit comprises reagents for isolation of cell-free DNA Attorney Docket No: 2014191-0041 (cfDNA) from a liquid biopsy sample. [0127] In some embodiments, a kit comprises reagents for library preparation for sequencing. [0128] In some embodiments, a kit comprises reagents for sequencing. [0129] In some embodiments, the present disclosure provides a non-transitory computer readable storage medium encoded with a computer program, wherein the program comprises instructions that when executed by one or more processors cause the one or more processors to perform operations to perform one or more method described herein. [0130] In some embodiments, the present disclosure provides a computer system comprising a memory and one or more processors coupled to the memory, wherein the one or more processors are configured to perform operations to perform one or more of the methods described herein. [0131] In some embodiments, the present disclosure provides a system for quantifying ER activity of a cancer in a subject, the system comprising a sequencer configured to generate a sequencing dataset from a sample; and a non-transitory computer readable storage medium and/or a computer system described herein. [0132] In some embodiments, a sequencer is configured to generate a Whole Genome Sequencing (WGS) dataset from the sample. [0133] In some embodiments, a system further comprises a sample preparation device configured to prepare a sample for sequencing from a biological sample, optionally a liquid biopsy sample. [0134] In some embodiments, a sample preparation device comprises reagents for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci in cell-free DNA (cfDNA) from the biological sample, optionally the liquid biopsy sample. [0135] In some embodiments, one or more genomic loci are selected from those listed in Tables 1, 2, 3, 4, 5, 6, 9, or 10. [0136] In some embodiments, a device comprises reagents for quantifying H3K4me3, Attorney Docket No: 2014191-0041 e.g., for: (a) at least 5, 10, 20, 30, or 38 genomic loci listed in Table 1; (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 3; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 4; or (d) any combination of (a)-(c). [0137] In some embodiments, a device comprises reagents for quantifying H3K27ac, e.g., for: (a) at least 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 2; (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 5; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 6; (d) at least 1, 5, 10, 20, 30, or 40 genomic loci listed in Table 9; (e) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 10; or (f) any combination of (a)-(e). [0138] In some embodiments, a system comprises reagents that comprise one or more antibodies for use in ChIP-seq, optionally wherein the one or more antibodies specifically bind H3K4me3- or H3K27ac-modified histones. [0139] In some embodiments, a device comprises reagents for isolation of cell-free DNA (cfDNA) from a biological sample, optionally a liquid biopsy sample. [0140] In some embodiments, a device comprises reagents for library preparation for sequencing. [0141] In some embodiments, a sequencer comprises reagents for sequencing. BRIEF DESCRIPTION OF THE DRAWING [0142] Fig.1 shows an outline of a comprehensive epigenomic platform that offers dynamic resolution into target and pathway biology from 1 mL of plasma. Cell free DNA derived from tumors exists in circulation as chromatin fragments that maintain tumor-associated epigenetic modifications on histones and DNA. Binding agents against, e.g., H3K27ac marking active enhancers, H3K4me3 marking active promoters and/or DNA methylation can be used to enrich for associated DNA fragments from a small volume of sample (e.g., 1 mL of plasma) and sequenced to define genome-wide epigenomic maps that capture the underlying Attorney Docket No: 2014191-0041 transcriptional state of tumor cells. [0143] Fig.2 shows an exemplary method for determining an ER activity score. Cell lines are treated with exogenous estrogen. Induced and repressed genes are identified using appropriate methods (e.g., RNA-seq, measuring genome wide promoter signal, enhancer signal, and/or DNA methylation, etc.). Promoter and enhancer signal associated with induced/repressed genes is quantified. An ER activity score can be determined, e.g., using the equation shown. In some embodiments, an ER activity score can be corrected for ctDNA%. [0144] Fig.3 shows that ER activity can be calculated independent of circulating tumor fraction. In (A), ER activity score (calculated, e.g., using methods described in Fig.1 and Examples 1 and 2) is plotted against ctDNA Fraction. As shown, a positive correlation was observed between ctDNA fraction and ER activity score for samples from ER+ patients but no relationship was observed in ER-negative samples. Light gray points (clustered around the top line, which was fit to the light gray points) correspond to samples obtained from ER+ patients, and black points (clustered around the bottom line, which was fit using the black points) correspond to samples obtained from ER-negative patients. (B) shows ctDNA corrected ER activity scores (generated by regressing ER activity score against ctDNA fraction). As shown in (B), samples from ER+ patients showed higher ER activity scores as compared to samples obtained from ER-negative patients. (C) shows exemplary promoter signal for ER-induced genes (not corrected for ctDNA%) observed in samples obtained from ER+ patients with a high ER expression (samples 1-4), samples from ER+ patients with a low ER expression (samples 5- 8), and samples from ER-negative patients (samples 9-10). As shown in (C), samples from ER+ patients with high ER expression showed higher promoter signal than samples from ER+ patients with a low ER expression score, and samples from ER-negative patients showed lower promoter signal as compared to samples from either group of ER+ patients, although the magnitude of difference in each case depended in part on ctDNA%. [0145] Fig.4 shows that ER+/HER2- patients display a range of ER activity scores. (A) shows ctDNA corrected ER activity score for (i) samples obtained from HER2-/ER-negative or HER2+/ER-negative subjects, and (ii) samples obtained from HER2-/ER+ and HER2+/ER+ patients. Samples from HER2+ samples showed consistently lower ER activity score, consistent with the understanding in the art that there is “crosstalk” between the ER and HER2 pathways when the two are co-expressed (e.g., as described in Pegram et al., NPJ Breast Cancer (2023) Attorney Docket No: 2014191-0041 9.1:45, the contents of which are incorporated by reference herein in their entirety). These results demonstrate, for the first time, that ER activity is lower in HER2+ patients (e.g., either through reorganization of the ER pathway or lower ER expression). (B) shows average Z-scores of Enhancer/Promoter signal in the enhancers and promoters of estrogen induced genes. Enhancer and promoter signal at genes including GREB1, ZNF703, and IGFBP4 drives in part the higher activity scores in ER+/HER2- patients. (C) shows average Z-scores of Enhancer/Promoter signal in the enhancers and promoters of estrogen repressed genes. Signal at enhancers and promoters of genes such as TGFB3, CCNG2, and PNPLA7 drives in part the lower activity scores of HER2+ patients. Boxed data indicates known ER induced or repressed genes. [0146] Fig.5 shows ER activity scores determined at multiple points in time. As shown in (A), ER activity scores were again found to be significantly higher in samples obtained from ER+ (IHC) patients as compared to samples obtained from ER-negative patients. This difference was observed in 3 patients who were ER+ on initial biopsy but had switched to ER-negative by the time of blood draw (circled), demonstrating that technologies provided herein are capable of detecting changes in ER activity score over time. (B) shows that mESR1 patients (mutant ESR1, corresponding to patients having an activating mutation in the ESR1 gene) exhibit consistently higher ER activity scores as compared to samples obtained from patients in which mutations associated with increased ER activity had not been detected or annotated. A subpopulation of patients in which no mutation had been detected exhibited high ER activity scores, suggesting that the technologies described in the present application can be used to identify further patients that would benefit from ER-targeted agents (e.g., SERDs). [0147] Fig.6 shows that patients with >4 lines of endocrine therapy displayed lower ER activity scores as compared to patients who received fewer lines of therapy. Shown are ctDNA- corrected ER activity scores stratified by number of endocrine therapy lines each patient had received at the time of blood draw. Patients who had received more therapies were found to exhibit lower ER activity scores, again showing that the technologies provided in the present application can detect biologically significant changes in a cancer, which can be useful, e.g., for informing treatment decisions. [0148] Fig.7 provides a table summarizing patient characteristics for the experiment Attorney Docket No: 2014191-0041 described in Example 5. [0149] Fig.8 provides exemplary ER+ breast cancer cell lines. Also indicated is PR and HER2 status. For each of the cell lines, RNA-seq, ChIP-seq for H3K27ac and H3K4me3 histone modifications, and MBD-seq was performed. “GoF” refers to Gain of Function. LoF refers to Loss of Function. [0150] Fig.9 provides RNA-seq data confirming activation of the ER signaling pathway in breast cancer cell lines upon E2 treatment. (A) provides a principal component analysis of cell line RNA-seq data, and shows clustering by cell line and stratification by HER2 status (see PC1 axis), as expected. Each cell line was tested in triplicate, for both conditions (exogenous estrogen and vehicle). (B) shows a differential expression analysis of cell lines treated with estrogen as compared to cell lines treated with vehicle. 799 genes were found to be upregulated by estrogen treatment, including known ER response genes, such as GREB1, ZNF703, and RERG. 592 genes were found to be upregulated by estrogen deprivation. DEseq2 is a computational package that can be used to perform differential signal analysis. By building models as “gene counts ~ cell line + treatment”, differential gene expression or enhancer counts are identified across treatments but conditioned on cell line ID, meaning that a gene/enhancer is required to have the same differential trend across all cell lines but each cell line is allowed to have a different y-intercept in the relationship between treatment and gene/enhancer counts. C) shows a gene set enrichment analysis of cell line RNA-seq data, and reveals an expected enrichment of estrogen response gene sets in cell lines exposed to exogenous estrogen. [0151] Fig.10 provides data showing characteristic epigenetic changes in breast cancer cell lines treated or deprived of estrogen. (A) provides MBD-seq results. Surprisingly, a differential DNA methylation analysis across estrogen exposed and deprived states revealed no significant differential DNA methylation sites. (B) provides a differential analysis of promoter signal (H3K4me3) across estrogen exposed and deprived states. Several hundred differentially modulated promoter regions were identified, including known ER response genes such as GREB1. (C) provides a gene set enrichment analysis of promoter signal (H3K4me3) with differential activity across estrogen exposed and deprived states. The analysis revealed an expected enrichment of estrogen response in estrogen exposed cells, in addition to upregulation of EMT pathway genes and downregulation of MYC target genes. (D) provides a differential analysis of enhancer signal (H3K27ac) across estrogen exposure states. Thousands of genome- Attorney Docket No: 2014191-0041 wide enhancers were found to be rearranged in response to exogenous estrogen exposure, including enhancers near known ER response genes like GREB1. (E) provides an ensemble analysis of eight breast cancer cell lines, enabling the identification of “core” ER responsive epigenomic patient samples. As shown, enhancer landscape rearrangement in response to estrogen exposure is highly cell type specific. (F) provides a gene set enrichment analysis of enhancer signal (H3K27ac) with differential activity across estrogen exposed and deprived states. The analysis revealed an expected enrichment of estrogen response in estrogen exposed cells. (G) provides a visualization of enhancer signal in Integrative Genomics View (IGV) for enhancers near known response genes, known breast cancer subtype marker genes, and housekeeping genes (each row indicates a different cell line). [0152] Fig.11. provides an illustration summarizing an exemplary method for measuring ER dependence (an ER dependence index), a measure of estrogen induced ER activity. The ER dependence index utilizes ER positive breast cancer patient plasma, cell line experiments, and previously annotated ER binding sites, FOXA1 binding sites, and genes associated with endocrine therapy resistance to measure estrogen dependent ER activation in a patient sample. Sequence reads of cfDNA comprising epigenetic modifications in patient plasma samples is measured (Step (1)). Sequence reads are then filtered, e.g., for peak segments that exhibit low signal in healthy patient samples and whose signal is correlated with estimated ctDNA% (Step(2)) and checked for overlap with regions that have been determined to exhibit changes in epigenetic modifications in cell lines treated with or deprived of estrogen (Step(3)). Loci are then screened for proximity to ER, FOXA1, and ET resistance genes and combined (Steps (4) and (5)). [0153] Fig.12 provides results from an experiment estimating the limit of quantification (LOQ) for methods described herein. Sequence reads obtained from ER+ (IHC) patient plasma samples were diluted in silico with sequence reads obtained from healthy patient plasma to generate data sets with different simulated ctDNA%. As shown, an LOQ of 2.15% ctDNA was estimated for methods described herein. [0154] Fig.13 shows the correlation between ER dependence as measured using H3K27ac modifications and ER activity as measured using RNA-seq, using a protocol described in Guan et al. (Guan et al., Cell (2019) 178(4):949-963), which had previously been shown to be predictive of clinical outcomes for patients treated with Giredestrant (Giredestrant is described, Attorney Docket No: 2014191-0041 e.g., in Collier, Ann, et al. "Exploratory biomarker analysis of acelERA breast cancer (BC): phase II study of gir-edestrant vs. physician’s choice of endocrine therapy (PCET) for previously treated, estrogen receptor-positive." HER2-negative advanced BC (ER+, HER2-aBC) (2023)). Estrogen-induced ER activity was measured using both methods, for each cell line, in both E2 supplemented and E2 stripped media. As shown, the two measures were found to correlate well with one another, demonstrating that methods described herein that utilize histone modifications to measure ER activity can provide accurate insights into intracellular dynamics and also can be used to predict responses to treatment and better inform therapy selection. [0155] Fig.14 provides enhancer signal at: (left panel) FOXA1-independent, ER-bound treatment induced enhancers; (center panel) FOXA1-bound, ER-independent E2 deprivation induced enhancers and (right panel) the difference of the values shown in the left and center panels. As shown, plasma samples from mESR1 patients consistently displayed higher ER activity and ER index scores and lower FOXA1 scores as compared to wtESR1 subjects. [0156] Fig.15 shows the correlation between ER dependence as measured by cfChIP and ER activity as determined using the RNA-seq based approach described in Guan et al., 2019, which had previously been shown to be predictive of clinical outcomes and a method described herein that utilizes histone modifications. As shown, the two measures were found to correlate well with one another, demonstrating that methods provided herein can accurately measure ER activity using cfDNA samples, and are therefore useful, e.g., for predicting patient responsiveness to therapies and guiding treatment selection. “TBD” and “Low Num + Den” indicate two samples for which there may be a discordance between the ER biology of biopsied tissue and a patient’s overall tumor burden. DETAILED DESCRIPTION [0157] The present disclosure is based, at least in part, on the demonstration that the ER activity of a cancer in a subject can be determined by detecting and quantifying the presence of histone modifications and/or DNA methylation at one or more genomic loci in cell-free DNA (cfDNA) from a liquid biopsy sample, e.g., a plasma sample obtained or derived from the subject. The present disclosure also encompasses methods where chromatin accessibility and/or binding of one or more transcription factors are detected at the one or more genomic loci instead of (or in addition to) histone modifications and/or DNA methylation. The present disclosure is Attorney Docket No: 2014191-0041 also based, at least in part, on the demonstration that genomic loci that are differentially modified based on different types of histone modifications (e.g., histone methylation marks such as H3K4me3 and histone acetylation marks such as H3K27ac) can be combined to result in an assay that can be used determine ER activity. These new assays provide minimally invasive ways of quantifying ER activity that are more accurate, objective, and comprehensive than current tissue-based approaches. No liquid biopsy platform to date has been able to provide actionable resolution on a transcriptionally regulated phenotype relevant for therapy such as ER activity. ER activity and cancer [0158] Estrogens are steroidal hormones that function as the primary female sex hormone. There are three major forms of estrogen, namely estrone (E1), estradiol (E2) and estriol (E3). Estradiol (E2) is the predominant estrogen in nonpregnant females, while estrone (E1) and estriol (E3) are primarily produced during pregnancy and following the onset of menopause, respectively. All estrogens are produced from androgens through actions of enzymes such as aromatase. Follicle-stimulating hormone and luteinizing hormone stimulate the synthesis of estrogen in the ovaries. However, some estrogens are also produced in smaller amounts by other tissues such as the liver, adrenal glands, and mammary gland. Studies have shown that estrogen is associated with mammary tumorigenesis, ovarian and endometrial carcinogenesis (Folkerd and Dowsett, J Clin Oncol (2010) 28:4038-4044). Also, mounting evidence suggests that estrogen and its target gene encoding progesterone receptor (PR) play critical roles in regulating breast cancer progression (Knutson et al., J Hematol Oncol (2017) 10:89). [0159] The biological effects of estrogen are mostly mediated by its binding and of the nuclear receptor superfamily of transcription factors that are characterized by highly conserved DNA- and ligand-binding domains (Wang et al., J Hematol Oncol (2017) 10:168). The DNA binding domain, which is distinct zinc finger motifs that are responsible for specific DNA binding, as well as mediating receptor dimerization (Hewitt and Korach, Endocr Rev (2018) 39(5):664-675). The unliganded ER has been shown to be present in a cytosolic complex with hsp90 and associated proteins, with Attorney Docket No: 2014191-0041 ligand binding allowing dissociation from the hsp90 complex, receptor dimerization, nuclear localization and binding to estrogen response elements (EREs) in promoters of estrogen- regulated genes (Pratt and Toft, Endocr Rev (1997) 18:306-360). Genome-wide chromatin immunoprecipitation studies have confirmed that the majority of ER-binding sites in estrogen responsive genes conform well to this consensus sequence (Welboren et al., EMBO J (2009) 28:1418-1428) target genes. e both unique and overlapping effects. [0160] heterodimerizing with other transcription factors such as activating protein 1 (AP1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). There is a large profile of estrogen-responsive genes, including pS2, cathepsin D, c-fos, c-jun, c-myc, TGF- -like growth factor 1 (IGF1) (Ikeda et al., Acta Pharmacol Sin (2015) 36:24-31). Many of these ER-regulated genes, including IGF1, cyclin D1, c-myc, and efp, are important for cell proliferation and survival. C-myc is a bona-fide oncogene that is amplified or overexpressed in a variety of human tumors. Efp is an ubiquitin ligase that promotes proteasomal degradation of 14-3-3 sigma thereby stimulating cellular proliferation. While PR is an estrogen- tumor growth, particularly through interacting with RNA polymerase III and inhibiting tRNA transcription. [0161] A (Adlanmerini et al., Proc Natl Acad Sci USA (2014) 111:E283-290), where it binds to diverse membrane or cytoplasmic signaling molecules such as the p85 regulatory subunit of class I phosphoinositide 3-kinase, mitogen-activated protein kinase (MAPK) and Src (Omarjee et al., Oncogene (2017) 36:2503-2514). Activation of these signal transduction pathways by estrogen initiates cell survival and proliferation signals. Additionally, these signaling molecules are able to -_{(Arnal et al.,} Physiol Rev (2017) 97:1045-1087). The genomic and non- role in breast epithelial cell proliferation and survival, as well as mammary tumorigenesis. The present application, inter alia, provides methods for detecting and quantifying aberrant activation Attorney Docket No: 2014191-0041 of estrogen receptors (e.g., ) via detection of pathway signaling activity in cancers (e.g., breast, ovarian and/or endometrial cancers). [0162] Based on the ER status, breast tumors can be classified as ER-positive or ER- is (Allred et al., Breast Cancer Res (2004) 6:240-245). To determine if a cancer is ER-positive, medical practitioners currently order testing that is conducted on a tissue sample using immunohistochemistry (IHC). Samples are reviewed by a pathologist and typically reported as (a) the word positive or negative, (b) a percentage that tells you how many cells out of 100 stained positive for hormone receptors, i.e., a number between 0% (none have receptors) and 100% (all have receptors), and/or (c) an Allred score between 0 and 8. The Allred scoring system looks at what percentage of cells test positive for hormone receptors, along with how well the receptors show up after staining, called intensity (Allred et al., Breast Cancer Res (2004) 6:240-245). This information is then combined to score the sample on a scale from 0 to 8 where, the higher the score, the more receptors were found and the easier they were to see in the sample. The terms “ER-positive” and “ER-negative” as used herein can correspond to any of these traditional approaches for determining ER status. [0163] Under current clinical protocols, ER-positive cancers can be treated with ER- targeted agents that lower estrogen levels or block estrogen binding to estrogen receptors. ER- positive cancers tend to grow more slowly than those that are ER-negative. Women with hormone receptor-positive breast cancers tend to have a better outlook in the short-term, but these cancers can sometimes come back many years after treatment. [0164] Treatment with ER-targeted agents is not helpful for ER-negative cancers. These cancers may instead be treated with one or more of surgery and/or radiation, HER2-targeted therapy (if HER2-positive), chemotherapy, and immunotherapy. If ER-negative cancers come back after treatment, it is often in the first few years. ER-negative breast cancers are more common in women who have not yet gone through menopause. [0165] ER expression status is not always a good predictor of responsiveness to ER- targeted therapies. Many subjects that initially respond well to ER-targeted agents exhibit reduced responsiveness over time (i.e., acquire resistance to ER-targeted agents). The mechanisms that drive resistance to ER-targeted agents are complex and varied and can include the mis-regulation of receptor tyrosine kinases (including, e.g., EGFR, PDGF, M-CSF, VEGF, Attorney Docket No: 2014191-0041 and HGF), transcription factors (e.g., SOX9 and other members of the HDAC family), cell cycle regulators, and autophagy. Further discussion of various mechanisms that can be associated with resistance to ER-targeted agents is provided in Yao, Jingwei, et al. "Progress in the understanding of the mechanism of tamoxifen resistance in breast cancer." Frontiers in pharmacology 11 (2020): 592912, the contents of which are incorporated by reference herein. Thus, treatments for ER+ cancers would benefit from the develop of methods that can measure ER activity and/or ER dependence (e.g., the degree to which a cancer is dependent on ER signaling activity for continued growth), which would be useful for better predicting responsiveness to ER-targeted agents and guiding therapy selection. [0166] Resistance to ER-targeted therapies has also been associated with FOXA1 activity. See, e.g., Cocce, Kimberly J., et al. "The lineage determining factor GRHL2 collaborates with FOXA1 to establish a targetable pathway in endocrine therapy-resistant breast cancer." Cell reports 29.4 (2019): 889-903, the contents of which are incorporated by reference herein in their entirety. Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene. FOXA1 is thought to potentially associated with poor outcomes and treatment resistance. Activity at many FOXA1 binding sites has been observed to increase as resistance to ER-targeted agents increases. See, e.g., Cocce et al. Some FOXA1 binding sites also overlap with ER binding sites. In some embodiments, methods provided herein adjust for FOXA1 activity by (i) not measuring enhancer signal at one or more genomic loci associated with (e.g., within about 2,000 bp of) a FOXA1 binding site that has previously been associated with increased resistance to an ER-targeted agent (e.g., tamoxifen), and/or (ii) adjusting for enhancer signal at one or more genomic loci associated with (e.g., within about 2,000 bp of) a FOXA1 binding site that has previously been associated with increased resistance to an ER-targeted agent (e.g., tamoxifen). In some embodiments, deconvolving increased promoter signal and/or enhancer signal at ER-specific sites from FOXA1-specific sites, an improved readout of ER activity that better excludes signal from a Attorney Docket No: 2014191-0041 mechanism for resistance to ER-targeted therapies can be achieved. ER-targeted agents [0167] The introduction of ER-targeted agents has dramatically influenced the outcome of patients with ER-positive breast cancers. ER-targeted agents block or degrade estrogen receptors or lower estrogen levels. Many ER-targeted agents have already been approved and others are in development or being tested in clinical trials for ER-positive breast cancer and other ER-positive cancers. Agents that block or degrade estrogen receptors (ER) [0168] These agents stop estrogen from fueling breast cancer cell growth. These agents work by preventing estrogen from activating estrogen receptors. They do this by blocking estrogen from binding to estrogen receptors or by degrading estrogen receptors. The former are called Selective Estrogen Receptor Modulators (SERMs) while the latter are called Selective Estrogen Receptor Degraders (SERDs). Selective Estrogen Receptor Modulators (SERMs) [0169] SERMs bind estrogen receptors and block them from binding to estrogen. These agents are typically pills, taken orally. Tamoxifen [0170] Tamoxifen can be used to treat women with breast cancer who have or have not gone through menopause. This agent can be used in several ways. In women at high risk of breast cancer, tamoxifen can be used to help lower the risk of developing breast cancer. [0171] For women who have been treated with breast-conserving surgery for ductal carcinoma in situ (DCIS) that is ER-positive, taking tamoxifen for 5 years lowers the chance of the DCIS coming back in the same breast. It also lowers the chance of getting an invasive breast cancer or another DCIS in both breasts. [0172] For women with ER-positive invasive breast cancer treated with surgery, tamoxifen can help lower the chances of the cancer coming back and improve the chances of living longer. It can also lower the risk of a new cancer developing in the other breast. Attorney Docket No: 2014191-0041 Tamoxifen can be started either after (adjuvant) or before (neoadjuvant) surgery. When given after surgery, it is usually taken for 5 to 10 years. This drug is used mainly for women with early-stage breast cancer who have not yet gone through menopause. If the subject has gone through menopause, aromatase inhibitors (see below) are often used instead. [0173] For women with ER-positive breast cancer that has spread to other parts of the body, tamoxifen can often help slow or stop the growth of the cancer and might even shrink some tumors. Toremifene [0174] Toremifene is a SERM that works in a similar way to tamoxifen, but it is used less often and is only approved to treat post-menopausal women with metastatic breast cancer. It is not likely to work if tamoxifen has already been used and has stopped working. Selective estrogen receptor degraders (SERDs) [0175] Like SERMs, these agents bind estrogen receptors but do so in a manner that causes them to be degraded. SERDs are used most often in post-menopausal women. When given to pre-menopausal women, they need to be combined with a luteinizing-hormone releasing hormone (LHRH) agonist to turn off the ovaries. Fulvestrant [0176] This ER-targeted agent can be used (i) alone to treat advanced breast cancer that has not been treated with other hormone therapy, (ii) alone to treat advanced breast cancer after other hormone drugs (like tamoxifen and often an aromatase inhibitor) have stopped working, or (iii) in combination with a CDK 4/6 inhibitor or PI3K inhibitor to treat metastatic breast cancer as initial hormone therapy or after other hormone treatments have been tried. It is given as two injections into the buttocks (bottom). For the first month, the two shots are given two weeks apart. After that, they are given once a month. Elacestrant [0177] This ER-targeted can be used to treat advanced, ER-positive, HER2-negative breast cancer when the cancer cells have an ESR1 gene mutation, and the cancer has grown after Attorney Docket No: 2014191-0041 at least one other type of hormone therapy. Elacestrant is taken daily as pills, orally. Drugs that lower estrogen levels [0178] Because estrogen stimulates ER-positive cancers to grow, lowering the estrogen level can help slow the cancer’s growth or help prevent it from coming back. Aromatase inhibitors (AIs) [0179] Aromatase inhibitors (AIs) are drugs that stop most estrogen production in the body. Before menopause, most estrogen is made by the ovaries. But in women whose ovaries are not working, either because they have gone through menopause or because of certain treatments, estrogen is still made in body fat by an enzyme called aromatase. AIs work by preventing aromatase from making estrogen. [0180] These drugs are useful for women who have gone through menopause, although they can also be used in pre-menopausal women when they are combined with ovarian suppression. These AIs are pills taken orally every day to treat breast cancer and include letrozole, anastrozole, and exemestane. Other ER-targeted agents and other cancers [0181] While the sections above focus on FDA approved ER-targeted agents, many other ER-targeted agents are being developed and/or assessed in clinical trials. It is to be understood that these other ER-targeted agents can also be used in treatment methods of the present disclosure. In addition, while the sections above focus on the treatment of ER-positive breast cancer, many of these ER-targeted agents can also be used to treat other ER-positive cancers, e.g., ovarian or endometrial ER-positive cancers. [0182] Additional ER-targeted agents include a Selective Estrogen Receptor Covalent Antagonist (SERCA), a Selective Human Estrogen Receptor Partial Agonist (ShERPA), or a combination thereof. [0183] Additional exemplary endocrine therapies (therapies that alter estrogen levels and/or block their effects on the body) for use in the methods described herein include, but are not limited to: anti-estrogens, for example, tamoxifen (including NOLVADEX® tamoxifen), raloxifene, droloxifene, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, Attorney Docket No: 2014191-0041 FARESTON® (toremifene citrate), nafoxidine, clomifene, anordrin, bazedoxifene, broparestrol, cyclofenil, lasofoxifene, ormeloxifene, acolbifene, elacestrant (RAD1901), clomifenoxide, etacstil, ospemifene, fulvestrant (FASLODEX®), EM800, brilanestrant (GDC- 0810), LX-039, AZ9496, GDC-0927 (SRN-0927); GDC-9545, G1T48 (Gl Therapeutics), H3B 6545 (H3 Biomedicine), SAR439859 (Sanofi), aromatase inhibitors that inhibit the enzyme aromatase, which regulates estrogen production in the adrenal glands, such as, for example, 4(5)- imidazoles, aminoglutethimide, MEGASE® megestrol acetate, AROMASIN® (exemestane), formestanie, fadrozole, RIVISOR® (vorozole), FEMARA® (letrozole), and ARIMIDEX® (anastrozole); anti-androgens such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; as well as troxacitabine (a l,3-dioxolane nucleoside cytosine analog); and antisense oligonucleotides, particularly those which inhibit expression of genes in signaling pathways implicated in aberrant cell proliferation, as well as combinations of two or more of the above. Subjects and Samples [0184] A sample analyzed using methods, kits and systems provided herein can be any biological sample including any processed sample that includes circulating tumor DNA (ctDNA) derived from a biological sample. In various embodiments, a sample analyzed using methods, kits and systems provided herein can be a sample obtained from a mammalian subject. In various embodiments, a sample analyzed using methods, kits and systems provided herein can be a sample obtained from a human subject. [0185] In various instances, a human subject is a subject diagnosed or seeking diagnosis as having, diagnosed as, or seeking diagnosis as at risk of having, and/or diagnosed as or seeking diagnosis as at immediate risk of having, an ER-positive cancer, e.g., ER-positive breast cancer, etc. In various instances, a human subject is a subject identified as needing ER status screening. In certain instances, a human subject is a subject identified as needing ER status screening by a medical practitioner. [0186] The subject may not have undergone previous treatments for cancer, such as the treatments recited in this disclosure. In other embodiments, the subject has undergone previous treatments for cancer, such as the treatments recited in this disclosure. [0187] In various embodiments a subject has one or more biomarkers and/or risk factors for cancer, e.g., ER-positive cancer, e.g., ER-positive breast cancer, etc. In certain embodiments, Attorney Docket No: 2014191-0041 a human subject is identified as in need of ER activity screening based on an initial cancer diagnosis, e.g., a breast cancer, etc. diagnosis. In various instances, a human subject is a subject not yet diagnosed as having, not at risk of having, not at immediate risk of having, not diagnosed as having, and/or not seeking diagnosis for a cancer. Genetic factors may also contribute to ER- positive cancer risk, as evidenced by individuals with a family history of ER-positive cancer. [0188] In various embodiments, a sample from a subject, e.g., a human, can be obtained from a liquid biopsy. In certain embodiments, a sample and/or reference is obtained from serum, plasma, or urine. In certain embodiments, the sample is serum. In certain embodiments, a sample comprises circulating tumor DNA (ctDNA). In certain embodiments, a sample is derived from about 1 mL of blood obtained from the subject. In certain embodiments, a sample is derived from about 0.5-2 mL of blood obtained from the subject, e.g., about 0.5 to 1.75 mL, about 0.5 to 1.5 mL, about 0.75 to 1.25 mL or about 0.9 to 1.1 mL of blood. [0189] In various embodiments, a sample is a sample of cell-free DNA (cfDNA). cfDNA is typically found in human biofluids (e.g., plasma, serum, or urine) in short, double- stranded fragments. The concentration of cfDNA is typically low, but can significantly increase under particular conditions, including without limitation pregnancy, autoimmune disorders, myocardial infarction, and cancer. Circulating tumor DNA (ctDNA) is the component of cell- free DNA specifically derived from cancer cells. ctDNA can be present in human biofluids bound to leukocytes and erythrocytes or not bound to leukocytes and erythrocytes. Various tests for detection of tumor-derived ctDNA are based on detection of genetic or epigenetic modifications that are characteristic of cancer (e.g., of a relevant cancer). Genetic or epigenetic factors characteristic of cancer can include, without limitation, oncogenic or cancer-associated mutations in tumor-suppressor genes, activated oncogenes, chromosomal disorders, histone modifications (e.g., histone methylation and/or histone acetylation), chromatin accessibility, binding of one or more transcription factors and/or DNA methylation. [0190] In various embodiments, ctDNA comprises less than 30%, less than 20%, or less than 10% of the cfDNA in the liquid biopsy sample obtained from the subject, e.g., less than 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or less than 1% of the cfDNA in the sample. In some embodiments, the percentage of ctDNA in the liquid biopsy sample is assessed using ichorCNA which estimates the percentage of ctDNA in a sample probabilistically (see Adalsteinsson et al., Nat Commun (2017) 8(1):1324 the entire contents of which are incorporated herein by Attorney Docket No: 2014191-0041 reference). [0191] cfDNA and ctDNA can provide a real-time or nearly real time metric of status of a source tissue. cfDNA and ctDNA demonstrate a half-life in blood of about 2 hours, such that a sample taken at a given time provides a relatively timely reflection of the status of a source tissue. [0192] Various methods of isolating nucleic acids from a sample (e.g., of isolating cfDNA from blood or plasma) are known in the art. Nucleic acids can be isolated using, without limitation, standard DNA purification techniques, by direct gene capture (e.g., by clarification of a sample to remove assay-inhibiting agents and capturing a target nucleic acid, if present, from the clarified sample with a capture agent to produce a capture complex and isolating the capture complex to recover the target nucleic acid). [0193] Reagents and protocols for obtaining and analyzing cfDNA and ctDNA, such as circulating in blood or other tissue, are commercially available as described in the Examples and well-known in the art (see, for example, Anker et al., Cancer and Metastasis Rev (1999) 18:65- 73; Wua et al., Clin Chim Acta (2002) 321:77-87; Fiegl et al., Cancer Res (2005) 15:1141-1145; Pathak et al., Clin Chem (2006) 52:1833-1842; Schwarzenbach et al., Clin Cancer Res (2009) 15:1032-1038; Schwarzenbach et al., Nat Rev Cancer (2011) 11:426-437) the contents of each of which is separately incorporated herein by reference in their entirety). [0194] In various embodiments, samples can be collected from individuals repeatedly over a period of time (e.g., once daily, weekly, monthly, annually, biannually, etc.). In various embodiments, such samples can be used to verify results from earlier detections and/or to identify an alteration in biological pattern because of, for example, disease progression, resistance to therapy, treatment, remission, and the like. For example, subject samples can be taken and monitored every month, every two months, or combinations of one, two, or three- month intervals according to the present disclosure. In various embodiments, samples can be collected for monitoring over time beginning at or at certain clinically determined stages, such as at resistance to a therapy, before radiographic progression, after radiographic progression, and/or at tissue biopsy. In addition, ER activity obtained at different points in time can be conveniently compared with each other, as well as with those of normal controls during the monitoring period, thereby providing the subject’s own values, as an internal, or personal, control for long-term Attorney Docket No: 2014191-0041 monitoring. [0195] Samples include materials prepared by processes including, without limitation, steps such as concentration, dilution, adjustment of pH, removal of high abundance polypeptides (e.g., albumin, gamma globulin, and transferrin, etc.), addition of preservatives, addition of calibrants, addition of protease inhibitors, addition of denaturants, desalting, concentration and/or extraction of sample nucleic acids, and/or amplification of sample nucleic acids (e.g., by PCR or other nucleic acid amplification techniques). Samples also include materials prepared by techniques that isolate, e.g., nucleosomes or transcription factors and/or nucleic acids associated with nucleosomes or transcription factors. [0196] Removal from a sample of proteins that are not desirable for a relevant purpose or context (e.g., high abundance, uninformative, or undetectable proteins) can be achieved using high affinity reagents, high molecular weight filters, ultracentrifugation and/or electrodialysis. High affinity reagents include antibodies or other reagents (e.g., aptamers) that selectively bind to high abundance proteins. Sample preparation can also include ion exchange chromatography, metal ion affinity chromatography, gel filtration, hydrophobic chromatography, chromatofocusing, adsorption chromatography, isoelectric focusing and related techniques. Molecular weight filters include membranes that separate molecules based on size and molecular weight. Such filters may further employ reverse osmosis, nanofiltration, ultrafiltration and microfiltration. Ultracentrifugation is the centrifugation of a sample at about 15,000-60,000 rpm while monitoring with an optical system the sedimentation (or lack thereof) of particles. Electrodialysis is a procedure which uses an electromembrane or semipermeable membrane in a process in which ions are transported through semi-permeable membranes from one solution to another under the influence of a potential gradient. Since the membranes used in electrodialysis may have the ability to selectively transport ions having positive or negative charge, reject ions of the opposite charge, or to allow species to migrate through a semipermeable membrane based on size and charge, it renders electrodialysis useful for concentration, removal, or separation of electrolytes. [0197] Separation and purification in the present disclosure may include any procedure known in the art, such as capillary electrophoresis (e.g., in capillary or on-chip) or chromatography (e.g., in capillary, column or on a chip). Electrophoresis is a method that can be used to separate ionic molecules under the influence of an electric field. Electrophoresis can be Attorney Docket No: 2014191-0041 conducted in a gel, capillary, or in a microchannel on a chip. Examples of gels used for electrophoresis include starch, acrylamide, polyethylene oxides, agarose, or combinations thereof. A gel can be modified by its cross-linking, addition of detergents, or denaturants, immobilization of enzymes or antibodies (affinity electrophoresis) or substrates (zymography) and incorporation of a pH gradient. Examples of capillaries used for electrophoresis include capillaries that interface with an electrospray. [0198] Capillary electrophoresis (CE) is preferred for separating complex hydrophilic molecules and highly charged solutes. CE technology can also be implemented on microfluidic chips. Depending on the types of capillary and buffers used, CE can be further segmented into separation techniques such as capillary zone electrophoresis (CZE), capillary isoelectric focusing (CIEF), capillary isotachophoresis (CITP) and capillary electrochromatography (CEC). An embodiment to couple CE techniques to electrospray ionization involves the use of volatile solutions, for example, aqueous mixtures containing a volatile acid and/or base and an organic such as an alcohol or acetonitrile. [0199] Capillary isotachophoresis (CITP) is a technique in which the analytes move through the capillary at a constant speed but are nevertheless separated by their respective mobilities. Capillary zone electrophoresis (CZE), also known as free-solution CE (FSCE), is based on differences in the electrophoretic mobility of the analytes, determined by the charge on the analytes, and the frictional resistance the analytes encounter during migration, which is often directly proportional to the size of the analytes. Capillary isoelectric focusing (CIEF) allows weakly-ionizable amphoteric molecules, to be separated by electrophoresis in a pH gradient. CEC is a hybrid technique between traditional high performance liquid chromatography (HPLC) and CE. [0200] Separation and purification techniques used in the present disclosure can include any chromatography procedures known in the art. Chromatography can be based on the differential adsorption and elution of certain analytes or partitioning of analytes between mobile and stationary phases. Different examples of chromatography include, but not limited to, liquid chromatography (LC), gas chromatography (GC), high performance liquid chromatography (HPLC), etc. [0201] In some embodiments, whole blood is collected from a subject, and a plasma layer is separated by centrifugation. cfDNA may be then extracted from the plasma using Attorney Docket No: 2014191-0041 methods known in the art. Histone Modifications, Chromatin Accessibility and Transcription Factor Binding [0202] Histone methylation is understood to increase or decrease expression of associated coding sequences, depending on which histone residue is methylated. Histone methylation is an essential modification that can cause monomethylation (me1), dimethylation (me2), and trimethylation (me3) of several amino acids, thus directly affecting heterochromatin formation, gene imprinting, X chromosome inactivation, and gene transcriptional regulation. Histone methyltransferases promote monomethylation, dimethylation, or trimethylation of histones while histone demethylases promote demethylation of histones. In general, lysine (Lys or K), arginine (Arg or R), and rarely histidine (His or H) are the most common histone methyl acceptors. Histone methylation only occurs at specific lysine and arginine sites of histone H3 and H4. In histone H3, lysine 4, 9, 26, 27, 36, 56, and 79 and arginine 2, 8, and 17 can be methylated. By comparison, histone H4 has fewer methylation sites, in which only lysine 5, 12, and 20 and arginine 3 can be methylated. Histone methylation is often associated with transcriptional activation or inhibition of downstream genes. The methylation of histone H3K4, R8, R17, K26, K36, K79, H4R3, and K12 can activate gene transcription. However, the methylation of histone H3K9, K27, K56, H4K5, and K20 can inhibit gene transcription. Thus, for example, H3K4 methylation generally activates gene expression, while H3K27 methylation generally represses gene expression. [0203] Histone acetylation occurs predominantly at lysine residues and is generally understood to increase expression of associated coding sequences. Without wishing to be bound by any theory, acetylation of lysine residues is thought to neutralize lysine’s positive charge and thereby cause histones to drift away from DNA, which has a negative charge. The released structure facilitates access to transcriptional machinery such as transcription factors and RNA polymerase II. Histone acetylation and deacetylation are generally catalyzed by histone acetyltransferases (HATs) and HDACs, respectively. Acetyl-CoA can be a source and co-factor of acetylation. In regulatory regions, HATs can acetylate histones and recruit HAT-containing complexes to activate the transcriptional process. For instance, H3K9ac and H3K27ac levels can be associated with promoter and enhancer activities. Furthermore, H3K27ac enhances not only the kinetics of transcriptional activation, but also accelerates the transition of RNA polymerase II Attorney Docket No: 2014191-0041 from the initiation state to the elongation state. [0204] Differential modification of a genomic locus (e.g., differential histone methylation and/or differential histone acetylation) can refer to, or be determined by or detected as, a comparative difference or change in modification status of one or more genomic loci between a first sample, condition, disease, or state and a second or reference sample, condition, disease, or state. Those of skill in the art will appreciate that a reference is typically produced by measurement using a methodology identical, similar, or comparable to that by which a compared non-reference measurement was taken. [0205] Chromatin accessibility can refer to the degree to which nuclear macromolecules are able to physically contact DNA and is determined in part by the occupancy and modification status of nucleosomes. Modified histones can regulate chromatin accessibility through a variety of mechanisms, such as altering transcription factor (TF) binding through steric hindrance and modulating nucleosome affinity for active chromatin remodelers. The topological organization of nucleosomes across the genome is non-uniform: while histones can be densely arranged within facultative and constitutive heterochromatin, histones can be depleted at regulatory loci, including within enhancers, insulators and transcribed gene bodies. Active regulatory elements of the genome are generally accessible. [0206] Differential accessibility of a genomic locus can refer to, or be determined by or detected as, a comparative difference or change in modification status of one or more genomic loci between a first sample, condition, disease, or state and a second or reference sample, condition, disease, or state. Those of skill in the art will appreciate that a reference is typically produced by measurement using a methodology identical, similar, or comparable to that by which a compared non-reference measurement was taken. [0207] A reference can be a value or set of values that are predetermined or derived from a sample or set of samples. A reference can be a sample or set of samples. A reference value can be a predetermined threshold value, a value that varies in accordance with circumstances (e.g., according to patient subpopulation, age, weight, or other variables), or a ratio. Reference ratios can be ratios relating to the modification and/or accessibility of multiple loci within individual samples and/or references, or across or between samples and/or references. In various embodiments, a reference can have or represent a normal, non-diseased state. In some embodiments, such as for staging of disease or for evaluating the efficacy of treatment, a Attorney Docket No: 2014191-0041 reference can have or represent a diseased state, e.g., a cancer, stage of cancer, or subtype of cancer, e.g., ER-positive cancer or ER-negative cancer. In some embodiments, a reference can represent an ER-positive (ER+) cancer with an Allred score of 3, 4, 5, 6, 7 or 8 based on IHC testing or an ER+ cancer with an Allred score of at least 3, at least 4, at least 5, at least 6, at least 7 or 8 based on IHC testing. In some embodiments, a reference can represent an ER- cancer with an Allred score of 0, 1, or 2 based on IHC testing. In some embodiments, a reference can correspond to a subject having breast cancer and/or a breast cancer subtype, e.g., ER-positive or ER-negative breast cancer. [0208] In certain instances, a reference is a non-contemporaneous sample from the same source, e.g., a prior sample from the same source, e.g., from the same subject. In certain instances, a reference for the modification status of one or more genomic loci (e.g., one or more differentially modified genomic loci) can be the modification status of the one or more genomic loci (e.g., one or more differentially modified genomic loci) in a sample (e.g., a sample from a subject), or a plurality of samples, known to represent a particular state (e.g., ER activity level). In certain instances, a reference for the accessibility status of one or more genomic loci (e.g., one or more differentially accessible genomic loci) can be the accessibility status of the one or more genomic loci (e.g., one or more differentially accessible genomic loci) in a sample (e.g., a sample from a subject), or a plurality of samples, known to represent a particular state (e.g., an ER- positive cancer or ER-negative cancer, a cell line treated with exogenous estrogen, a cell line cultivated in media that lacks estrogen, or a cell line deprived of estrogen). [0209] In some illustrative but non-limiting embodiments of the present disclosure differential modification or differential accessibility can refer to a differential (e.g., between a sample and a reference) with an absolute log2(fold-change) that is greater than or equal to 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0 or more, or any range in between, inclusive, e.g., as measured according to an assay provided herein. [0210] Enhancers are genomic loci that can be differentially modified or differentially accessible in and/or between conditions, diseases, and other states. Enhancers are cis-acting DNA regulatory regions that are thought to bind trans-acting proteins that contribute to expression patterns of associated genes. Chromatin ImmunoPrecipitation sequencing (ChIP-seq) of histone modifications (e.g., acetylation) have identified millions of enhancers in mammalian genomes. The number of active enhancers in any given cell type is estimated to be in the tens of Attorney Docket No: 2014191-0041 thousands. Certain transcription factors (TFs), sometimes referred to as “master” transcription factors, associate with active enhancers with important impacts on gene expression and cell function. Certain such transcription factors preferentially associate with enhancers that regulate genes required for establishing cell identity and function, including enhancer domains known as “super-enhancers”. Moreover, master TFs can participate in inter-connected auto-regulatory circuitries or “cliques” that are self-reinforcing, show marked cell selectivity, and function to maintain cell state and/or cell survival. Techniques for Detecting and Quantifying Histone Modifications and Transcription Factor Binding [0211] Various techniques of molecular biology are well known in the art and/or disclosed in the present application for detecting and quantifying histone modifications and/or transcription factor binding. In some embodiments, the methods, kits and systems of present disclosure involve the detection and quantification of histone modifications and/or transcription factor binding in samples, e.g., in liquid biopsy samples including cfDNA such as plasma samples including cfDNA. Chromatin ImmunoPrecipitation (ChIP) is one technique of molecular biology useful in detecting and quantifying histone modifications and transcription factor binding in samples. CUT&RUN or CUT&Tag are other more recent techniques that can also be used to detect and quantify histone modifications and transcription factor binding sites. ChIP-chip, ChIP-exo, ChIP Re-ChIP, and ChIPmentation are other alternative techniques that could be used. [0212] ChIP can involve various steps including one or more of fixation, sonication, immunoprecipitation, and analysis of the immunoprecipitated DNA. ChIP has become a very widely used tissue-based technique for determining the in vivo location of binding sites of various transcription factors and histones. Because the proteins are captured at the sites of their binding with DNA, ChIP helps to detect DNA-protein interactions that take place in living cells. More importantly, ChIP can be coupled to many commonly used molecular biology techniques such as PCR and real-time PCR, PCR with single-stranded conformational polymorphism, Southern blot analysis, Western blot analysis, cloning, and microarray. The resulting versatility has increased the potential of this technique. [0213] ChIP of tissue samples usually involves cross-linking of the chromatin-bound Attorney Docket No: 2014191-0041 proteins by formaldehyde, followed by sonication or nuclease treatment to obtain small DNA fragments. Immunoprecipitation can be then carried out using specific antibodies to the DNA- binding protein of interest. The DNA can be then released from the proteins and analyzed using various methods. ChIP has also been used to study RNA-protein interactions. X-ChIP methods utilize fixed chromatin fragmented by sonication, while the N-ChIP methods utilize native chromatin, which can be unfixed and nuclease digested. [0214] The first step of the technique can be the cross-linking of DNA and proteins. Formaldehyde is one of the most used cross-linking agents. One advantage of using formaldehyde can be the ease of reversibility of the cross-links and its ability to form bonds that span approximately 2 angstroms. This means that formaldehyde can bind molecules in close association with each other. Generally, formaldehyde can be added to the medium in the cell culture flask or plate. It enters the cells through the cell membrane and cross-links the proteins to the chromatin. Formaldehyde fixation of tumor tissues has also been done. Other cross- linking agents that have been used include chemicals such as methylene blue and acridine orange, cisplatin, dimethylarsinic acid, potassium chromate, and ultraviolet (UV) light and lasers. [0215] Harvested chromatin can be sonicated in one or more sonication cycles. DNA can be typically broken into 100–500 bp fragments to pinpoint the location of the DNA sequence of interest. An alternative to sonication can be nuclease digestion of the chromatin, e.g., in N-ChIP methods. Purification of chromatin can be achieved using a cesium chloride (CsCl) gradient centrifugation. [0216] Chromatin can be immunoprecipitated using one or more antibodies that bind a target epitope. For example, an antibody used in ChIP can selectively bind a particular transcription factor or one or more particular histone modifications, such as one or more particular histone acetylation modifications or histone methylation modifications. In some embodiments, an antibody used to bind a target epitope can be a “pan” antibody (e.g., a pan- acetylation antibody, a pan-methylation antibody, an antibody that binds a group of histone modifications associated with increased transcription activation, and/or an antibody that binds a group of histone modifications associated with increased transcription repression). The antibody against the protein of interest is allowed to bind to the protein-DNA complex, and the complex can be then precipitated. Immunosorbants commonly used to separate the antigen-antibody complex from the lysate include salmon sperm DNA-protein A-Sepharose®, protein G, magnetic Attorney Docket No: 2014191-0041 beads, and other engineered immunoprecipitation systems known to those of skill in the art. [0217] Immunoprecipitated DNA can be eluted. Once the DNA of interest is isolated, many detection and quantification methods can be used to study the isolated gene fragments. Commonly utilized methods include PCR, real-time PCR, slot blot hybridization, microarray techniques, and deep or next-generation sequencing. ChIP-seq combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing to identify the binding sites of DNA-associated proteins. ChIP-seq can be used to map DNA-binding proteins, e.g., transcription factor binding sites and histone modifications in a genome-wide manner. [0218] Cell-free Chromatin ImmunoPrecipitation sequencing (cfChIP-seq) involves applying ChIP-seq to samples that include cell-free DNA, e.g., liquid biopsy samples including cfDNA such as plasma samples including cfDNA (e.g., see Sadeh et al., Nat Biotechnol (2021) 39: 586–598 and Jang et al., Life Sci Alliance (2023) 6(12):e202302003 the entire contents of each of which are incorporated herein by reference). In some embodiments, cfChIP-seq uses antibodies or antibody fragments that bind specific histone modifications (e.g., H3K4me3 and/or H3K27ac) and/or transcription factors that are coupled (covalently or non-covalently) to beads, e.g., magnetic beads such as Dynabeads® magnetic beads and incubated with a volume, e.g., about 1 mL of thawed plasma obtained from a subject. Without limitation, exemplary antibodies that bind H3K4me3 include PA5-27029 (available from Thermo Fisher Scientific in Waltham, MA) and C15410003 (available from Diagenode in Denville, NJ) and exemplary antibodies that bind H3K27ac include ab21623 or ab4729 (both available from Abcam in Cambridge, UK) and C15210016 (available from Diagenode in Denville, NJ). [0219] In some embodiments, the antibodies or antibody fragments can be covalently coupled to beads, e.g., epoxy beads. In some embodiments, the antibodies or antibody fragments can be non-covalently coupled to beads, e.g., Protein A or Protein G beads such as Dynabeads® Protein A or Dynabeads® Protein G beads. After washing, a cfDNA library is then typically prepared from the captured cfDNA. Library preparation can be done on-bead or after releasing the captured cfDNA by digestion of bound histones, e.g., using proteinase K. The cfDNA library is then sequenced to generate reads of captured cfDNA sequences, e.g., by next-generation sequencing (NGS) as is known in the art. The reads are then analyzed, e.g., aligned and counted using standard bioinformatic techniques as is known in the art. A cfChIP-seq bioinformatic pipeline can include, e.g., alignment of sequence reads to a reference genome with BWA or Attorney Docket No: 2014191-0041 Bowtie2. Aligned reads can be used to call and quantify peaks as compared to a reference. [0220] CUT&Tag involves antibody-based binding of a target protein, e.g., transcription factor or histone modification of interest, where antibody incubation is directly followed by the shearing of the chromatin and library preparation (see Kaya-Okur et al., Nat Comm (2019) 10:1930). CUT&Tag assays take advantage of a Tn5 transposase that is fused with Protein A to direct the enzyme to the antibody bound to its target on chromatin. Tn5 transposase is pre- loaded with sequencing adapters (generating the assembled pA-Tn5 adapter transposome) to carry out antibody-targeted tagmentation. In a typical CUT&Tag assay samples are incubated with an antibody immobilized on Concanavalin A-coated magnetic beads to facilitate subsequent washing steps. Cells can be incubated with a primary antibody specific for the target protein of interest followed by incubation with a secondary antibody. Samples can then be incubated with assembled transposomes, which consist of Protein A fused to the Tn5 transposase enzyme that is conjugated to NGS adapters. After incubation, unbound transposome can be washed away using stringent conditions. Tn5 is a Mg²⁺-dependent enzyme so Mg²⁺ can be added to activate the reaction, which results in the chromatin being cut close to the protein binding site and simultaneous addition of the NGS adapter DNA sequences. Chromatin cleavage and library preparation can be achieved in one single step. [0221] CUT&RUN is an epigenomic profiling strategy in which antibody-targeted controlled cleavage by micrococcal nuclease releases specific protein-DNA complexes into the supernatant for paired-end DNA sequencing (see Skene and Henikoff, Elife (2017) 6:1-35, Skene et al., Nat Protoc (2018) 13:1006-1019). As only targeted fragments enter into solution, and the vast majority of DNA is left behind, CUT&RUN has low background levels. In an example CUT&RUN assay, a sample is incubated with an antibody or antibody fragment that binds the target protein, e.g., transcription factor or histone modification of interest. The sample is then incubated with Protein-A-MNase after which CaCl2 can be added to initiate the calcium dependent nuclease activity of MNase to cleave the DNA around the target protein. The protein- A-MNase reaction can be quenched by adding chelating agents (EDTA and EGTA). Cleaved DNA fragments are then liberated, extracted, and used to construct a sequencing library. Techniques for Detecting and Quantifying Chromatin Accessibility [0222] Various techniques of molecular biology are well known in the art and/or Attorney Docket No: 2014191-0041 disclosed in the present application for detecting and quantifying chromatin accessibility. In some embodiments, the methods, kits and systems of the present disclosure involve the detection and quantification of chromatin accessibility in samples, e.g., in liquid biopsy samples including cfDNA such as plasma samples including cfDNA. ATAC-seq (Assay of Transpose Accessible Chromatin sequencing), NOMe-seq (Nucleosome Occupancy and Methylome sequencing), FAIRE-seq (Formaldehyde-Assisted Isolation of Regulatory Elements sequencing), MNase-seq (Micrococcal Nuclease digestion with sequencing), and DNase hypersensitivity assays are exemplary techniques of molecular biology useful in detecting and quantifying chromatin accessibility in samples. Sono-Seq is another alternative method that could be used (see Auerbach et al., Proc Natl Acad USA (2009) 106(35):14926-14931). Fragmentomics-based methods are yet another method that can be used to assess chromatin accessibility (see Ding, Spencer C., and YM Dennis Lo. "Cell-free DNA fragmentomics in liquid biopsy." Diagnostics 12.4 (2022): 978). [0223] DNase hypersensitivity assays can use the non-specific DNA endonuclease Deoxyribonuclease I (DNase I), which selectively digests accessible DNA regions. DNase I hypersensitivity sites (DHS) identified by DNase-seq include open chromatin regulatory regions. A typical DNase hypersensitivity assay can include a first step in which nuclei are isolated from cells using lysis buffer, and nuclei are digested using DNase I. DNA fragment sizes are measured to identify optimal digestion using gel electrophoresis. Biotinylated linkers can be ligated to the ends of digested DNA after polishing to make blunt ends, and the DNA can then be isolated. DNA with biotinylated linker can be digested by restriction endonuclease MmeI and captured by streptavidin coated Dynabeads® to generate short tags to which a second sequencing adaptor can be ligated. A second linker can be ligated and amplified to generate a library for sequencing. A DNase-seq bioinformatic pipeline can include, e.g., alignment of sequence reads to a reference genome with BWA or Bowtie2. Aligned reads can be used to call and quantify peaks as compared to a reference. [0224] MNase-seq determines chromatin accessibility with micrococcal nuclease (MNase) that preferentially digests nucleosome-free, protein-unbound DNA. A typical MNase- seq assay can include a first step in which nuclei are isolated from either native or crosslinked chromatin and digested using MNase with titration. In vivo formaldehyde crosslinking step that is designed to capture the interaction between proteins and DNA. This crosslinking allows Attorney Docket No: 2014191-0041 bound proteins to shield their associated DNA from digestion by MNase. Following crosslinking, samples are digested with MNase, which can be specifically activated by addition of Ca2+ to the buffer. Digestion can be halted by chelating the reaction, at which point the samples are RNase treated, crosslinks are reversed, and proteins are digested away from the chromatin. DNA can then be isolated via a phenol-chloroform extraction. Uncut DNA is purified and mononucleosome bands are isolated and excised through gel electrophoresis. Isolated DNA can be amplified by adding adapters to generate a library, and sequenced. MNase- seq primarily sequences regions of DNA bound by histones or other proteins. Therefore, it indirectly determines which regions of DNA are accessible by directly determining which regions are bound to nucleosomes or proteins. [0225] FAIRE-seq is a method in which nucleosome-depleted regions of DNA (NDRs) are isolated from chromatin. A typical FAIRE-seq assay can include a first step in which cells are fixed using formaldehyde so that histones are crosslinked to interacting DNA. Crosslinked chromatin can then be sheared by sonication that generates protein-free DNA and protein- crosslinked DNA fragments. Protein-free DNA can be isolated using a phenol–chloroform extraction: DNA crosslinked with protein stays in organic phase, while protein-free DNA stays in aqueous phase. Highly crosslinked DNA remains in the organic phase and the non- crosslinked DNA is pulled to the aqueous phase. Non-crosslinked DNA from the aqueous phase can then be amplified and sequenced. Reads enriched in the sequencing pool tend to have lower nucleosome and transcription factor binding and are therefore inferred to come from accessible regions. [0226] NOMe-seq is a method to identify nucleosome-depleted regions of DNA (NDRs) with M.CviPI methyltransferase that methylates cytosine in GpC dinucleotides not protected by nucleosomes or other proteins. Unlike C^mpG, GpC^m in the human genome does not occur naturally in most cell types. GpC^m levels at open chromatin regions can be compared to background signals and used to detect and quantify NDRs. A typical NOMe-seq protocol can include a step in which samples are treated with M.CviPI and S-adenosylhomocysteine (SAM) to methylate accessible GpC sites. M.CviPI treated DNA can be sheared using a sonicator, so that DNA fragments can be sequenced. DNA is treated with bisulfite, which converts unmethylated cytosine to uracil using sodium bisulfite, while methylated cytosine is unaffected. A library is generated using adapters and sequenced. Accessible chromatin is expected to have high levels of Attorney Docket No: 2014191-0041 GpC^m but low levels of C^mpG. Therefore, NOMe-seq identifies NDRs using the two separate methylation analyses that serve as independent (but opposite) measures, providing matched chromatin designations for each regulatory element. [0227] ATAC-seq uses hyperactive Tn5 transposase that preferentially cuts accessible chromatin regions and simultaneously inserts adapters to the fragmented region (Buenrostro et al., Nat Methods (2013) 10(12):1213-1218 the entirety of which is incorporated herein by reference). A typical ATAC-seq assay can include a first step in which samples are incubated with Tn5 transposase. DNA can then be isolated and purified. DNA fragmented and tagged by Tn5 transposase can be purified and then amplified to generate a library and sequenced for analysis. Techniques for Detecting and Quantifying DNA Methylation [0228] Various techniques of molecular biology are well known in the art and/or disclosed in the present application for detecting and quantifying DNA methylation. In some embodiments, the methods, kits and systems of the present disclosure involve the detection and quantification of chromatin accessibility in samples, e.g., in liquid biopsy samples including cfDNA such as plasma samples including cfDNA. Bisulfite sequencing (BS-Seq), Whole Genome Bisulfite Sequencing (WGBS), Methylated DNA ImmunoPrecipitation sequencing (MeDIP-seq), or Methyl-CpG-Binding Domain sequencing (MBD-seq) are exemplary techniques of molecular biology useful in detecting and quantifying chromatin accessibility in samples. Reduced representation bisulfite sequencing (RRBS) is another alternative method that could be used (see Meissner et al., Nucleic Acids Res (2005) 33(18):5868-5877). Illumina Infinium arrays could also be used to detect and quantify DNA methylation. [0229] DNA methylation typically refers to the methylation of the 5’ position of cytosine (mC) by DNA methyltransferases (DNMT). It is a major epigenetic modification in humans and many other species. In mammals, most DNA methylations occur within the context of CpG dinucleotides. DNA methylation is thought to be a repressive chromatin modification. Aberrant methylation can lead to many diseases including cancers (Robertson, Nat Rev Genet (2005) 6:597–610 and Bergman and Cedar, Nat Struct Mol Biol (2013) 20:274–281). [0230] Bisulfite sequencing (BS-Seq) or Whole-Genome Bisulfite Sequencing (WGBS) is a well-established protocol to detect methylated cytosines in genomic DNA. In this method, genomic Attorney Docket No: 2014191-0041 DNA is treated with sodium bisulfite and then sequenced, providing single-base resolution of methylated cytosines in the genome. Upon bisulfite treatment, unmethylated cytosines are deaminated to uracils which, upon sequencing, are converted to thymidines. Simultaneously, methylated cytosines resist deamination and are read as cytosines. The location of the methylated cytosines can then be determined by comparing treated and untreated sequences. [0231] MeDIP-seq was first reported by Weber et al., Nat Genet (2005) 37:853–862. In a typical MeDIP-seq protocol, antibody or antibody-fragment that binds 5-methylcytidine (5mC) is used to enrich methylated DNA fragments, then these fragments are sequenced and analyzed. If using 5mC-specific antibodies or antibody fragments, methylated DNA is isolated from genomic DNA via immunoprecipitation. Anti-5mC antibodies are incubated with fragmented genomic DNA and precipitated, followed by DNA purification and sequencing. [0232] Methyl-CpG-Binding Domain sequencing (MBD-seq) is similar to MeDIP-seq except that it uses methyl binding domain (MBD) proteins instead of antibodies or antibody fragments to bind methylated DNA. In a typical MBD-seq protocol, genomic DNA is first sonicated and incubated with tagged MBD proteins that can bind methylated cytosines. The protein-DNA complex is then precipitated with antibody-conjugated beads that are specific to the MBD protein tag, followed by DNA purification and sequencing. Classifiers [0233] In some embodiments, the present disclosure provides methods for obtaining a classifier, e.g., a classifier that can be used to determine ER status. In some embodiments, a subject is determined to have an epigenetic profile indicative of an ER-positive cancer based on analysis of a biological sample, optionally of cell-free DNA (cfDNA) from a liquid biopsy sample, obtained or derived from the subject. In some embodiments, a cancer is determined to be ER-positive if an ER activity is detected that is above a threshold value. In some embodiments, the threshold value is a predetermined threshold and/or a normalized value. In some embodiments, the threshold value is an ER pathway activity score determined in a reference population. In some embodiments, the reference population comprises subjects having cancer and previously found to respond to treatment with an ER-targeted therapy. In some embodiments, the reference population comprises subjects having cancer and previously found to not respond to treatment with an ER-targeted therapy, and wherein the threshold value is greater Attorney Docket No: 2014191-0041 than the ER activity score determined in the reference population. In some embodiments, the reference population comprises subjects having an ER-positive cancer (e.g., as determined by IHC). In some embodiments, the reference population comprises subjects having an ER- negative cancer (e.g., as determined by IHC) or determined to be cancer free, and the threshold value is an ER activity score that is greater than the ER activity score determined in the reference population. [0234] “Fragmentomics” or a “fragmentomics assay” refers to methods that use certain size and sequence characteristics of cfDNA to gain insight into the epigenetic state of cells at the time their genomic DNA was released into the extracellular environment. Without wishing to be bound by theory, upon release of genomic DNA from a cell into the extracellular environment, nucleases rapidly cleave the genomic DNA into short fragments. The cleavage pattern and sequences of the fragments reflect the positioning of nucleosomes genome-wide at the point of cell death, and by finding nucleosomes that are consistently genomically positioned across cancer cells (i.e. many of the circulating tumor DNA fragments that map to that small region of the genome have the same start and end positions or similar fragment length characteristics) fragmentomics attempts to infer the location of stably positioned nucleosomes at regulatory sites, and thus to infer where the active regulatory sites are in a given cell type. Accordingly, analysis of cfDNA fragmentation patterns can be used to infer characteristics of the cells at the time they released genomic DNA. Examples of metrics commonly used in fragmentomics include fragment size, preferred ends, end motifs, single-stranded jagged ends, and nucleosomal footprints. Approaches for measuring fragmentomics metrics include, e.g., qPCR, electron microscopy, single molecule sequencing, and next-generation sequencing. A relationship between fragmentomic metrics and histone modifications (h3K4me3 and H3K27ac) has been established. See Bai, Jinyue, et al. "Histone modifications of circulating nucleosomes are associated with changes in cell-free DNA fragmentation patterns." Proceedings of the National Academy of Sciences 121.42 (2024): e2404058121. In some embodiments, one or more fragmentomics metrics and one or more histone modifications (e.g., H3K27ac) are measured at one or more genomic loci described herein. Exemplary Genomic Loci [0235] The present disclosure includes the identification of exemplary genomic loci that Attorney Docket No: 2014191-0041 are differentially modified and/or differentially accessible depending on ER activity in a cancer. Tables 1-6, 9, and 10 show chromosomal coordinates of genomic loci whose epigenomic modifications can change depending on ER activity. In Table 1, “promoter” indicates a locus associated with a promoter region of the indicated gene. In Table 2 “enhancer” indicates a locus associated with an enhancer region of the indicated gene. “Induced” refers to a gene whose expression is increased upon activation of the ER signaling pathway, whereas “repressed” refers to a gene whose expression is decreased upon stimulation of the ER signaling pathway. [0236] The present disclosure is not limited to methods that use the exact same chromosomal coordinates that are recited in Tables 1-6, 9, and 10. The present disclosure encompasses methods that use any of the genomic loci in Tables 1-6, 9, and 10 and also subregions thereof, i.e., references herein to methods that involve detecting and/or quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci of Tables 1-6, 9, and 10 encompasses methods that detect these marks anywhere within these genomic loci including within any subregions. For example, where Table 1 references chr1:109791640-109793641 as a genomic locus for detecting and/or quantifying promoter signal (e.g., H3K4me3 modification), this encompasses methods that detect and/or quantify H3K4me3modification at any position or sub-region of chr1:109791640-109793641, e.g., methods that detect and/or quantify H3K4me3modification within chr1:109792640-109793441, etc. In some embodiments, a subregion may span at least 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500 or at least 3000 contiguous base pairs that are located between the lower and upper coordinates of a genomic locus recited in Tables 1-6, 9, or 10. In some embodiments, a subregion may span less than 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500 or at least 3000 contiguous base pairs that are located between the lower and upper coordinates of a genomic locus recited in Tables 1-6, 9, or 10. In some embodiments, a subregion may have the same central coordinate as a genomic locus recited in Tables 1-6, 9, or 10. In some embodiments, a subregion may have a different central coordinate as a genomic locus recited in Tables 1-6, 9, or 10. It is also to be understood that the lower/upper coordinates of the genomic loci in Tables 1-6, 9, and 10 are approximate and that the present disclosure encompasses methods where any one or more of the genomic loci are expanded by increasing the size of the genomic locus by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or up to 50% in one or both directions. The present Attorney Docket No: 2014191-0041 disclosure also encompasses methods that use genomic loci that are associated with one or more of the genes listed in Tables 1 and 2, including, e.g., loci that are not recited in Tables 1-6, 9, and 10. [0237] In some embodiments an assay for determining ER activity is generated using a set of differentially modified and/or differentially accessible genomic loci that are correlated with activation of the ER signaling pathway. Sequence reads that fall into each selected genomic locus are analyzed and counted, e.g., as described herein including in the Examples. [0238] In some embodiments, ER pathway activity can be determined by quantifying a single type of histone modification at one or more of the loci listed in Tables 1-6, 9, or 10 (e.g., quantifying H3K4me3 modifications at one or more loci listed in Table 1, 3, or 4 or quantifying H3K27ac modifications at one or more loci listed in Table 2, 5, 6, 9, or 10). In some embodiments, ER pathway activity can be determined by quantifying multiple types of histone modifications (e.g., H3K4me3 and H3K27ac) at one or more of the loci listed in Table 1, one or more of the loci listed in Table 2, one or more of the loci listed in Table 3, one or more of the loci listed in Table 4, one or more of the loci listed in Table 5, one or more of the loci listed in Table 6, one or more of the loci listed in Table 9, and/or one or more of the loci listed in Table 10 (e.g., quantifying H3K4me3 modifications at one or more loci listed in Table 1 and quantifying H3K27ac modifications at one or more loci listed in Table 2). Differential H3K4me3 modification [0239] Genomic loci demonstrating differential H3K4 methylation (in particular H3K4 trimethylation, H3K4me3) depending on activation of the ER signaling pathway in a cancer are provided in Tables 1 and 3, which shows chromosomal coordinates of genomic loci. Genomic loci demonstrating increased H3K4 methylation (in particular H3K4 trimethylation, H3K4me3) in cell lines deprived of estrogen are provided in Table 4, which shows chromosomal coordinates of genomic loci. [0240] In various embodiments, methods described herein comprise quantifying H3K4me3 modifications in a promoter associated with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the genes listed in Table 1 (or any subset thereof). In certain embodiments, a method comprises quantifying H3K4me3 modifications in a promoter of one or more genes listed in Table 1 (or any subset thereof) having (i) a lower bound selected from about Attorney Docket No: 2014191-0041 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, or about 15 and (ii) an upper bound selected from about 10, about 15, or about 20. In some embodiments, a method comprises quantifying H3K4me3 modifications in a promoter of about 1 to about 21, about 5 to about 21, about 10 to about 21, or about 15 to about 21 genes listed in Table 1. [0241] In various embodiments, methods described herein comprise quantifying H3K4me3 modifications in a promoter associated with one (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 125, about 150, about 175, about 200, or about 225) or more (e.g., all) of the genes listed in Table 3 (or any subset thereof). In certain embodiments, a method comprises quantifying H3K4me3 modifications in a promoter of one or more genes listed in Table 3 (or any subset thereof) having (i) a lower bound selected from about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, or about 200 and (ii) an upper bound selected from about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, about 200, or about 225). In some embodiments, a method comprises quantifying H3K4me3 modifications in a promoter of about 1 to about 100, about 5 to about 100, about 10 to about 100, about 50 to about 100, about 100 to about 200, about 1 to about 200, about 5 to about 200, about 10 to about 200, or about 50 to about 200 genes listed in Table 3. [0242] In various embodiments, methods described herein comprise quantifying H3K4me3 modifications in a promoter associated with one (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 125, about 150, about 175, about 200, about 225, about 250, about 275, about 300, or about 325) or more (e.g., all) of the genes listed in Table 4 (or any subset thereof). In certain embodiments, a method comprises quantifying H3K4me3 modifications in a promoter of one or more genes listed in Table 3 (or any subset thereof) having (i) a lower bound selected from about 1, about 2, about 3, about 4, about 5, about Attorney Docket No: 2014191-0041 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, or about 200 and (ii) an upper bound selected from about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, about 175, about 200, about 225, about 205, about 275, or about 300). In some embodiments, a method comprises quantifying H3K4me3 modifications in a promoter of about 1 to about 100, about 5 to about 100, about 10 to about 100, about 50 to about 100, about 100 to about 200, about 1 to about 200, about 5 to about 200, about 10 to about 200, or about 50 to about 200 genes listed in Table 4. [0243] In some embodiments, a method comprises quantifying H3K4me3 modifications in a promoter of at least about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 75%, or about 100% of the genes listed in Table 1, 3, or 4. In some embodiments, responsiveness to a cancer therapeutic can be predicted using a method that comprises quantifying H3K4me3 modifications in a promoter of a percent of genes listed in Table 1, 3, or 4 having a lower bound of about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, or about 10%, and an upper bound of about 1%, about 2%, about 3%, about 4%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 75%, or about 100%. [0244] A person of skill in the art will recognize that the methods disclosed herein do not require that every genomic locus listed in Table 1, 3, or 4 be assessed for H3K4me3 modification. Instead, a subset of loci may be assessed for H3K4me3 modification. Subsets of the genomic loci of Table 1, 3, or 4 can be selected (e.g., for use in determining ER activity) based on various performance criteria, e.g., to select genomic loci that demonstrate differential modification with a particular level of statistical significance and/or a particular threshold of differential between relevant states (e.g., a measured log2(fold-change)). Subsets of the genomic loci may also be selected based on an algorithm, e.g., during the process of obtaining a classifier. Those of skill in the art will appreciate that such subsets of loci of Table 1, 3, or 4, and loci included in such subsets, are together, individually, and/or in randomly selected subsets, at least as informative (e.g., as statistically significant and/or reliable) for uses disclosed herein, e.g., for Attorney Docket No: 2014191-0041 quantifying ER pathway activity. [0245] In various embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in using at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, or 35 of the loci identified in Table 1 (or any subset thereof). In certain embodiments, ER pathway activity in cancer in a subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least a number of loci identified in a Table 1 (or any subset thereof) having a lower bound selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, or 35 and an upper bound selected from 10, 15, 20, 25, 30, 35, or 38. In certain particular embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least 1, 2, 3, 4, 5, 10, 20, 30, 35 or 38 loci identified in Table 1 (e.g., about 1 to about 38, about 5 to about 38, about 10 to about 38, about 25 to about 38, about 5, about 10, about 20, or about 38 loci). In various embodiments ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100% of loci identified in Table 1. In certain embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in a percent of loci identified in Table 1 having a lower bound selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, or 10%, and an upper bound selected from 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100%. [0246] In various embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in using at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 of the loci identified in Table 3 (or any subset thereof). In certain embodiments, ER pathway activity in cancer in a subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least a number of loci identified in a Table 3 (or any subset thereof) having a lower bound selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 and an upper bound selected from 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 125, 150, 175, 200, 225, 250, 276, 300, or 325. In certain particular embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least 1, 2, 3, 4, 5, 10, 20, 30, 35, 40, 45, 50, 60, 70, 80, 90 or 100 loci identified in Table 3 Attorney Docket No: 2014191-0041 (e.g., about 1 to about 100, about 5 to about 100, about 10 to about 100, about 25 to about 100, about 5, about 10, about 20, about 25, about 30, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 loci). In various embodiments ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100% of loci identified in Table 3. In certain embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in a percent of loci identified in Table 3 having a lower bound selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, or 10%, and an upper bound selected from 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100%. [0247] In various embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in using at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 of the loci identified in Table 4 (or any subset thereof). In certain embodiments, ER pathway activity in cancer in a subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least a number of loci identified in a Table 4 (or any subset thereof) having a lower bound selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 and an upper bound selected from 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 125, 150, 175, 200, 225, 250, 276, 300, or 325, 350, 375, 400, 425, 450, 475, or 500. In certain particular embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least 1, 2, 3, 4, 5, 10, 20, 30, 35, 40, 45, 50, 60, 70, 80, 90 or 100 loci identified in Table 4 (e.g., about 1 to about 100, about 5 to about 100, about 10 to about 100, about 25 to about 100, about 5, about 10, about 20, about 25, about 30, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 loci). In various embodiments ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100% of loci identified in Table 4. In certain embodiments, ER pathway activity in a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K4me3 modifications in a percent of loci identified in Table 4 having a lower Attorney Docket No: 2014191-0041 bound selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, or 10%, and an upper bound selected from 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100%. [0248] In various embodiments, differentially H3K4me3 modified refers to a methylation status characterized by an increase or decrease in a value measuring methylation (e.g., of read counts and/or normalized read counts for a given genomic locus), and/or a mean, median and/or mode thereof, and/or a log thereof (e.g., log base 2 (log2)), of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 75%, 100%, 2-fold, 3-fold, 4- fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 35-fold, 40- fold, 45-fold, 50-fold, or greater, or any range in between, inclusive, such as 1% to 50%, 50% to 2-fold, 25% to 50-fold, 25% to 30-fold, 25% to 20-fold, 25% to 16-fold, 30% to 16-fold, 50% to 16-fold, 70% to 16-fold, 2-fold to 16-fold, 2.2-fold to 16-fold, 2.6-fold to 16-fold, 3-fold to 16- fold, 3.4-fold to 16-fold, 4-fold to 16-fold, 4.5-fold to 16-fold, 5.2-fold to 16-fold, 6-fold to 16- fold, 7-fold to 16-fold, or 8-fold to 16-fold, as compared to a reference, optionally where the statistical significance of the increase or decrease is at least 5e-2, 1e-2, 5e-3, 1e-3, 5e-4, 1e-4, 5e- 5, 1e-5, 5e-6, or 1e-6. In various embodiments, an increase or decrease in a value measuring methylation can be, or is expressed as, a log2(fold-change), e.g., a log2(fold-change) of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 75%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, or greater, or any range in between, inclusive, such as an increase or decrease of 0.1-fold to 10- fold, 0.2-fold to 5-fold, 0.2-fold to 4.0-fold, 0.4-4.0-fold, 0.4-fold to 4.0-fold, 0.6-fold to 4.0- fold, 0.8-fold to 4.0-fold, 1.0-fold to 4.0-fold.1.2-fold to 4.0-fold.1.4-fold to 4.0-fold, 1.6-fold to 4.0-fold, 1.8-fold to 4.0-fold, 2.0-fold to 4.0-fold, 2.2-fold to 4.0-fold, 2.4-fold to 4.0-fold, 2.6- fold to 4.0-fold, 2.8-fold to 4.0-fold, or 3.0-fold to 4.0-fold, optionally where the statistical significance of the increase or decrease is at least 5e-2, 1e-2, 5e-3, 1e-3, 5e-4, 1e-4, 5e-5, 1e-5, 5e-6, or 1e-6. [0249] In some embodiments, H3K4me3 modifications are quantified for loci listed in Table 3 that have an absolute log2(fold-change) of 2.2 or higher, 2.0 or higher, 1.9 or higher, 1.8 or higher, 1.7 or higher, 1.6 or higher, 1.5 or higher, 1.4 or higher, 1.3 or higher, 1.2 or higher, 1.1 or higher, 1.0 or higher, 0.9 or higher, 0.8 or higher, 0.7 or higher, 0.6 or higher, or 0.5 or higher. The present disclosure also includes subsets of the genomic loci of Table 4, which have an absolute log2(fold-change) of 2.2 to less than 2.4, 2.0 to less than 2.2, 1.8 to less than 2.0, 1.6 Attorney Docket No: 2014191-0041 to less than 1.8, 1.4 to less than 1.6, 1.2 to less than 1.4, 1.0 to less than 1.2, 0.8 to less than 1.0, 0.6 to less than 0.8, or 0.5 to less than 0.6. [0250] In some embodiments, H3K4me3 modifications are quantified for loci listed in Table 4 that have an absolute log2(fold-change) of 2.2 or higher, 2.0 or higher, 1.9 or higher, 1.8 or higher, 1.7 or higher, 1.6 or higher, 1.5 or higher, 1.4 or higher, 1.3 or higher, 1.2 or higher, 1.1 or higher, 1.0 or higher, 0.9 or higher, 0.8 or higher, 0.7 or higher, 0.6 or higher, or 0.5 or higher. The present disclosure also includes subsets of the genomic loci of Table 4, which have an absolute log2(fold-change) of 2.2 to less than 2.4, 2.0 to less than 2.2, 1.8 to less than 2.0, 1.6 to less than 1.8, 1.4 to less than 1.6, 1.2 to less than 1.4, 1.0 to less than 1.2, 0.8 to less than 1.0, 0.6 to less than 0.8, or 0.5 to less than 0.6. Differential H3K27ac modification [0251] Genomic loci that can comprise differential H3K27ac modification in cancers depending on activation of the ER signaling pathway are provided in Tables 2, 5, 6, 9, and 10 which show the chromosomal coordinates of each genomic locus that can be differentially modified depending on the extent of activation of the ER signaling pathway. [0252] In various embodiments, methods described herein comprise quantifying H3K27ac modifications in a promoter associated with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the genes listed in Table 2 (or any subset thereof). In certain embodiments, a method comprises quantifying H3K27ac modifications in a promoter of one or more genes listed in Table 2 (or any subset thereof) having (i) a lower bound selected from about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, or about 15 and (ii) an upper bound selected from about 10, about 15, or about 20. In some embodiments, a method comprises quantifying H3K27ac modifications in a promoter of about 1 to about 21, about 5 to about 21, about 10 to about 21, or about 15 to about 21 genes listed in Table 2. [0253] In various embodiments, methods described herein comprise quantifying H3K27ac modifications in an enhancer associated with one (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 125, about 150, about 175, about 200, about 225, about 250, about 275, about 300, about 350, about 400, about 450, about 500, about 550, Attorney Docket No: 2014191-0041 about 600, about 650, about 700, about 750, about 800, about 850, about 900, about 950, about 1000, about 1050, about 1100, about 1150, about 1200, about 1250, about 1300, about 1350, about 1400, about 1450, or about 1500) or more (e.g., all) of the genes listed in Table 5 (or any subset thereof). In certain embodiments, a method comprises quantifying H3K27ac modifications in an enhancer of one or more genes listed in Table 5 (or any subset thereof) having (i) a lower bound selected from about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, or about 200 and (ii) an upper bound selected from about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, about 175, about 200, about 225, about 250, about 275, or about 300). In some embodiments, a method comprises quantifying H3K27ac modifications in an enhancer of about 1 to about 100, about 5 to about 100, about 10 to about 100, about 50 to about 100, about 100 to about 200, about 1 to about 200, about 5 to about 200, about 10 to about 200, about 50 to about 200, about 100 to about 200, 1 to about 500, about 5 to about 500, about 10 to about 500, about 50 to about 500, about 100 to about 500, about 200 to about 500, 1 to about 1000, about 5 to about 1000, about 10 to about 1000, about 50 to about 1000, about 100 to about 1000, about 200 to about 1000, about 500 to about 1000, 1 to about 1500, about 5 to about 1500, about 10 to about 1500, about 50 to about 1500, about 100 to about 1500, about 200 to about 1500, about 500 to about 1500, or about 1000 to about 1500 genes listed in Table 5. [0254] In various embodiments, methods described herein comprise quantifying H3K27ac modifications in an enhancer associated with one (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 125, about 150, about 175, about 200, about 225, about 250, about 275, about 300, about 350, about 400, about 450, about 500, about 550, about 600, about 650, about 700, about 750, about 800, about 850, about 900, about 950, about 1000, about 1050, about 1100, about 1150, about 1200, about 1250, about 1300, about 1350, about 1400, about 1450, about 1500, about 1550, about 1600, about 1650, about 1700, or about 1750) or more (e.g., all) of the genes listed in Table 6 (or any subset thereof). In certain Attorney Docket No: 2014191-0041 embodiments, a method comprises quantifying H3K27ac modifications in an enhancer of one or more genes listed in Table 6 (or any subset thereof) having (i) a lower bound selected from about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, or about 200 and (ii) an upper bound selected from about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, about 175, about 200, about 225, about 205, about 275, or about 300). In some embodiments, a method comprises quantifying H3K27ac modifications in an enhancer of about 1 to about 100, about 5 to about 100, about 10 to about 100, about 50 to about 100, about 100 to about 200, about 1 to about 200, about 5 to about 200, about 10 to about 200, about 50 to about 200, about 100 to about 200, 1 to about 500, about 5 to about 500, about 10 to about 500, about 50 to about 500, about 100 to about 500, about 200 to about 500, 1 to about 1000, about 5 to about 1000, about 10 to about 1000, about 50 to about 1000, about 100 to about 1000, about 200 to about 1000, about 500 to about 1000, 1 to about 1500, about 5 to about 1500, about 10 to about 1500, about 50 to about 1500, about 100 to about 1500, about 200 to about 1500, about 500 to about 1500, or about 1000 to about 1500 genes listed in Table 6. [0255] In various embodiments, methods described herein comprise quantifying H3K27ac modifications in an enhancer associated with one (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, or about 65 of the genes listed in Table 7 (or any subset thereof). In certain embodiments, a method comprises quantifying H3K27ac modifications in an enhancer of one or more genes listed in Table 7 (or any subset thereof) having (i) a lower bound selected from about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, or about 65, and (ii) an upper bound selected from about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, or about 65). In some embodiments, a method comprises quantifying H3K27ac modifications in an enhancer of about 1 to about 60, about 5 to about 60, about 10 to about 60, about 50 to about 60, about 1 to about 50, about 5 to about 50, about 10 to about 50, 1 to about Attorney Docket No: 2014191-0041 25, about 5 to about 25, about 10 to about 25, 1 to about 20, about 5 to about 20, or about 10 to about 20 genes listed in Table 7. [0256] In various embodiments, methods described herein comprise quantifying H3K27ac modifications in an enhancer associated with one (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 125, about 150, about 175, about 200, about 225, or about 250) or more (e.g., all) of the genes listed in Table 8 (or any subset thereof). In certain embodiments, a method comprises quantifying H3K27ac modifications in an enhancer of one or more genes listed in Table 8 (or any subset thereof) having (i) a lower bound selected from about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, or about 200 and (ii) an upper bound selected from about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, about 175, about 200, about 225, or about 250). In some embodiments, a method comprises quantifying H3K27ac modifications in an enhancer of about 1 to about 100, about 5 to about 100, about 10 to about 100, about 50 to about 100, about 100 to about 200, about 1 to about 200, about 5 to about 200, about 10 to about 200, or about 50 to about 200 genes listed in Table 8. [0257] In some embodiments, a method comprises quantifying H3K4me3 modifications in a promoter of at least about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 75%, or about 100% of the genes listed in Table 2, 5, 6, 7, or 8. In some embodiments, responsiveness to a cancer therapeutic can be predicted using a method that comprises quantifying H3K4me3 modifications in a promoter of a percent of genes listed in Table 2, 5, 6, 7, or 8 having a lower bound of about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, or about 10%, and an upper bound of about 1%, about 2%, about 3%, about 4%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 75%, or about 100%. [0258] A person of skill in the art will recognize that the methods disclosed herein do not Attorney Docket No: 2014191-0041 require that every genomic locus listed in Tables 2, 5, 6, 9, and 10 be assessed for H3K27ac modification. Instead, a subset of loci may be assessed for H3K27ac modification. Subsets of the genomic loci of Tables 2, 5, 6, 9, and 10 can be selected (e.g., for use in quantifying ER pathway activity) based on various performance criteria, e.g., to select genomic loci that demonstrate differential modification with a particular level of statistical significance and/or a particular threshold of differential between relevant states (e.g., a measured log2(fold-change)). Subsets of the genomic loci may also be selected based on an algorithm. Those of skill in the art will appreciate that such subsets of loci of Tables 2, 5, 6, 9, and 10, and loci included in such subsets, are together, individually, and/or in randomly selected subsets, at least as informative (e.g., as statistically significant and/or reliable) for uses disclosed herein, e.g., for determining ER pathway activity. [0259] In various embodiments, the ER pathway activity of a sample or subject from which the sample is obtained or derived, can be determined by quantifying H3K27ac modifications at at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, or 300 of the loci listed in Table 2 (or any subset thereof). In certain embodiments, ER activity in a cancer in a subject from which the sample is obtained or derived, is determined by quantifying H3K27ac modifications at at least a number of loci identified in a Table 2 (or any subset thereof) having a lower bound selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, or 300 and an upper bound selected from 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 300, or 340. In certain particular embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined to by quantifying H3K27ac modifications for at least 1, 2, 3, 4, 5, 10, 20, 30, 40, or 50 or more loci identified in Table 2 (e.g., about 1 to about 300, about 5 to about 300, about 10 to about 300, about 25 to about 200, about 5, about 10, about 20, or about 50 loci). In various embodiments ER activity of a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K27ac modification of at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100% of loci identified in Table 2. In certain embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K27ac modifications using at least a percent of loci identified in Table 2 having a lower bound selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, or 10%, and an upper bound Attorney Docket No: 2014191-0041 selected from 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100%. [0260] In various embodiments, the ER pathway activity of a sample or subject from which the sample is obtained or derived, can be determined by quantifying H3K27ac modifications at at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, or 300 of the loci listed in Table 5 (or any subset thereof). In certain embodiments, ER activity in a cancer in a subject from which the sample is obtained or derived, is determined by quantifying H3K27ac modifications at at least a number of loci identified in a Table 5 (or any subset thereof) having a lower bound selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, or 300 and an upper bound selected from 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 300, 500, 750, 1000, 1250, 1500, 1750, 2000, 2250, 2500, 2750, or 3000. In certain particular embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined to by quantifying H3K27ac modifications for at least 1, 2, 3, 4, 5, 10, 20, 30, 40, or 50 or more loci identified in Table 5 (e.g., about 1 to about 300, about 5 to about 300, about 10 to about 300, about 25 to about 200, about 5, about 10, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 loci). In various embodiments ER activity of a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K27ac modification of at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100% of loci identified in Table 5. In certain embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K27ac modifications using at least a percent of loci identified in Table 5 having a lower bound selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, or 10%, and an upper bound selected from 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100%. [0261] In various embodiments, the ER pathway activity of a sample or subject from which the sample is obtained or derived, can be determined by a method that comprises quantifying H3K27ac modifications at at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, or 300 of the loci listed in Table 6 (or any subset thereof). In certain embodiments, ER activity in a cancer in a subject from which the sample is obtained or derived, is determined by a method that comprises quantifying H3K27ac modifications at at least a number of loci identified in a Table 6 (or any subset thereof) Attorney Docket No: 2014191-0041 having a lower bound selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, or 300 and an upper bound selected from 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 300, 500, 750, 1000, 1250, 1500, 1750, 2000, 2250, 2500, 2750, or 3000. In certain particular embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined to by a method that comprises quantifying H3K27ac modifications for at least 1, 2, 3, 4, 5, 10, 20, 30, 40, or 50 or more loci identified in Table 6 (e.g., about 1 to about 300, about 5 to about 300, about 10 to about 300, about 25 to about 200, about 5, about 10, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 loci). In various embodiments ER activity of a sample or subject from which the sample is obtained or derived, is determined by a method that comprises quantifying H3K27ac modification of at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100% of loci identified in Table 6. In certain embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined by a method that comprises quantifying H3K27ac modifications using at least a percent of loci identified in Table 6 having a lower bound selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, or 10%, and an upper bound selected from 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100%. [0262] In various embodiments, the ER pathway activity of a sample or subject from which the sample is obtained or derived, can be determined by quantifying H3K27ac modifications at at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, or 40 of the loci listed in Table 9 (or any subset thereof). In certain embodiments, ER activity in a cancer in a subject from which the sample is obtained or derived, is determined by quantifying H3K27ac modifications at at least a number of loci identified in a Table 9 (or any subset thereof) having a lower bound selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, or 35 and an upper bound selected from 10, 15, 20, 25, 30, 35, or 40. In certain particular embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined to by quantifying H3K27ac modifications for at least 1, 2, 3, 4, 5, 10, 20, 30, or 40 or more loci identified in Table 9 (e.g., about 1 to about 300, about 5 to about 300, about 10 to about 300, about 25 to about 200, about 5, about 10, about 20, or about 50 loci). In various embodiments ER activity of a sample or subject from which the sample is obtained or derived, is determined Attorney Docket No: 2014191-0041 by quantifying H3K27ac modification of at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100% of loci identified in Table 9. In certain embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined by quantifying H3K27ac modifications using at least a percent of loci identified in Table 9 having a lower bound selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, or 10%, and an upper bound selected from 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100%. [0263] In various embodiments, the ER pathway activity of a sample or subject from which the sample is obtained or derived, can be determined by a method that comprises quantifying H3K27ac modifications at at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or 145 of the loci listed in Table 10 (or any subset thereof). In certain embodiments, ER activity in a cancer in a subject from which the sample is obtained or derived, is determined by a method that comprises quantifying H3K27ac modifications at at least a number of loci identified in a Table 10 (or any subset thereof) having a lower bound selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 and an upper bound selected from 10, 15, 20, 25, 50, 75, 100, or 145. In certain particular embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined by a method that comprises quantifying H3K27ac modifications for at least 1, 2, 3, 4, 5, 10, 20, 30, 40, or 50 or more loci identified in Table 10 (e.g., about 1 to about 140, about 5 to about 145, about 10 to about 100, about 25 to about 100, about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 loci). In various embodiments ER activity of a sample or subject from which the sample is obtained or derived, is determined by a method that comprises quantifying H3K27ac modification of at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, or 100% of loci identified in Table 10. In certain embodiments, ER pathway activity of a sample or subject from which the sample is obtained or derived, is determined by a method that comprises quantifying H3K27ac modifications using at least a percent of loci identified in Table 10 having a lower bound selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, or 10%, and an upper bound selected from 1%, 2%, 3%, 4%, 5%, 10%, 20%, Attorney Docket No: 2014191-0041 30%, 40%, 50%, 75%, or 100%. [0264] In various embodiments, differentially H3K27ac modified refers to an acetylation status characterized by an increase or decrease in a value measuring acetylation (e.g., of read counts and/or normalized read counts for a given genomic locus), and/or a mean, median and/or mode thereof, and/or a log thereof (e.g., log base 2 (log2)), of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 75%, 100%, 2-fold, 3-fold, 4- fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 35-fold, 40- fold, 45-fold, 50-fold, or greater, or any range in between, inclusive, such as 1% to 50%, 50% to 2-fold, 25% to 50-fold, 25% to 30-fold, 25% to 20-fold, 25% to 16-fold, 30% to 16-fold, 50% to 16-fold, 70% to 16-fold, 2-fold to 16-fold, 2.2-fold to 16-fold, 2.6-fold to 16-fold, 3-fold to 16- fold, 3.4-fold to 16-fold, 4-fold to 16-fold, 4.5-fold to 16-fold, 5.2-fold to 16-fold, 6-fold to 16- fold, 7-fold to 16-fold, or 8-fold to 16-fold, as compared to a reference, optionally where the statistical significance of the increase or decrease is at least 5e-2, 1e-2, 5e-3, 1e-3, 5e-4, 1e-4, 5e- 5, 1e-5, 5e-6, or 1e-6. In various embodiments, an increase or decrease in a value measuring acetylation can be, or is expressed as, a log2(fold-change), e.g., a log2(fold-change) of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 75%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, or greater, or any range in between, inclusive, such as an increase or decrease of 0.1-fold to 10- fold, 0.2-fold to 5-fold, 0.2-fold to 4.0-fold, 0.4-4.0-fold, 0.4-fold to 4.0-fold, 0.6-fold to 4.0- fold, 0.8-fold to 4.0-fold, 1.0-fold to 4.0-fold.1.2-fold to 4.0-fold.1.4-fold to 4.0-fold, 1.6-fold to 4.0-fold, 1.8-fold to 4.0-fold, 2.0-fold to 4.0-fold, 2.2-fold to 4.0-fold, 2.4-fold to 4.0-fold, 2.6- fold to 4.0-fold, 2.8-fold to 4.0-fold, or 3.0-fold to 4.0-fold, optionally where the statistical significance of the increase or decrease is at least 5e-2, 1e-2, 5e-3, 1e-3, 5e-4, 1e-4, 5e-5, 1e-5, 5e-6, or 1e-6. [0265] In some embodiments, H3K27ac modifications are quantified for loci listed in Table 5 that have an absolute log2(fold-change) of 4.0 or higher, 3.8 or higher, 3.6 or higher, 3.4 or higher, 3.2 or higher, 3.0 or higher, 2.8 or higher, 2.6 or higher, 2.4 or higher, 2.2 or higher, 2.0 or higher, 1.9 or higher, 1.8 or higher, 1.7 or higher, 1.6 or higher, 1.5 or higher, 1.4 or higher, 1.3 or higher, 1.2 or higher, 1.1 or higher, 1.0 or higher, 0.9 or higher, 0.8 or higher, 0.7 or higher, 0.6 or higher, or 0.5 or higher. The present disclosure also includes subsets of the genomic loci of Table 5, which have an absolute log2(fold-change) of 4.0 to less than 4.1, 3.8 to Attorney Docket No: 2014191-0041 less than 4.0, 3.6 to less than 3.8, 3.4 to less than 3.6, 3.2 to less than 3.4, 3.0 to less than 3.2, 2.8 to less than 3.0, 2.6 to less than 2.8, 2.4 to less than 2.6, 2.2 to less than 2.4, 2.0 to less than 2.2, 1.8 to less than 2.0, 1.6 to less than 1.8, 1.4 to less than 1.6, 1.2 to less than 1.4, 1.0 to less than 1.2, 0.8 to less than 1.0, 0.6 to less than 0.8, or 0.5 to less than 0.6. [0266] In some embodiments, H3K27ac modifications are quantified for loci listed in Table 6 that have an absolute log2(fold-change) of 3.6 or higher, 3.4 or higher, 3.2 or higher, 3.0 or higher, 2.8 or higher, 2.6 or higher, 2.4 or higher, 2.2 or higher, 2.0 or higher, 1.9 or higher, 1.8 or higher, 1.7 or higher, 1.6 or higher, 1.5 or higher, 1.4 or higher, 1.3 or higher, 1.2 or higher, 1.1 or higher, 1.0 or higher, 0.9 or higher, 0.8 or higher, 0.7 or higher, 0.6 or higher, or 0.5 or higher. The present disclosure also includes subsets of the genomic loci of Table 6, which have an absolute log2(fold-change) of3.6 to less than 3.8, 3.4 to less than 3.6, 3.2 to less than 3.4, 3.0 to less than 3.2, 2.8 to less than 3.0, 2.6 to less than 2.8, 2.4 to less than 2.6, 2.2 to less than 2.4, 2.0 to less than 2.2, 1.8 to less than 2.0, 1.6 to less than 1.8, 1.4 to less than 1.6, 1.2 to less than 1.4, 1.0 to less than 1.2, 0.8 to less than 1.0, 0.6 to less than 0.8, or 0.5 to less than 0.6. [0267] As described in the Examples of the present disclosure, genomic loci listed in Tables 5-6, 9, and 10 were identified, in part, through analysis of a plurality of cell lines. Without wishing to be bound by theory, epigenetic modification can vary between different cell lines. Thus, loci described herein, identified across a plurality of cell lines better capture heterogeneity in the epigenomic landscape, and more widely applicable to a variety of samples. Differential DNA methylation [0268] In various embodiments, differentially DNA methylated refers to a methylation status characterized by an increase or decrease in a value measuring methylation (e.g., of read counts and/or normalized read counts for a given genomic locus), and/or a mean, median and/or mode thereof, and/or a log thereof (e.g., log base 2 (log2)), of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 75%, 100%, 2-fold, 3-fold, 4- fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 35-fold, 40- fold, 45-fold, 50-fold, or greater, or any range in between, inclusive, such as 1% to 50%, 50% to 2-fold, 25% to 50-fold, 25% to 30-fold, 25% to 20-fold, 25% to 16-fold, 30% to 16-fold, 50% to 16-fold, 70% to 16-fold, 2-fold to 16-fold, 2.2-fold to 16-fold, 2.6-fold to 16-fold, 3-fold to 16- fold, 3.4-fold to 16-fold, 4-fold to 16-fold, 4.5-fold to 16-fold, 5.2-fold to 16-fold, 6-fold to 16- Attorney Docket No: 2014191-0041 fold, 7-fold to 16-fold, or 8-fold to 16-fold, as compared to a reference, optionally where the statistical significance of the increase or decrease is at least 5e-2, 1e-2, 5e-3, 1e-3, 5e-4, 1e-4, 5e- 5, 1e-5, 5e-6, or 1e-6. In various embodiments, an increase or decrease in a value measuring methylation can be, or is expressed as, a log2(fold-change), e.g., a log2(fold-change) of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 75%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, or greater, or any range in between, inclusive, such as an increase of 0.1-fold to 10-fold, 0.2-fold to 5-fold, 0.2-fold to 4.0-fold, 0.4-4.0-fold, 0.4-fold to 4.0-fold, 0.6-fold to 4.0-fold, 0.8-fold to 4.0-fold, 1.0-fold to 4.0-fold.1.2-fold to 4.0-fold.1.4-fold to 4.0-fold, 1.6-fold to 4.0-fold, 1.8- fold to 4.0-fold, 2.0-fold to 4.0-fold, 2.2-fold to 4.0-fold, 2.4-fold to 4.0-fold, 2.6-fold to 4.0-fold, 2.8-fold to 4.0-fold, or 3.0-fold to 4.0-fold, optionally where the statistical significance of the increase or decrease is at least 5e-2, 1e-2, 5e-3, 1e-3, 5e-4, 1e-4, 5e-5, 1e-5, 5e-6, or 1e-6. Differential chromatin accessibility or transcription factor binding [0269] Genomic loci provided in Tables 1-3, 5-7, 9 can demonstrate differential chromatin accessibility or transcription factor binding in cancers depending on the extent of activation of the ER signaling pathway. Tables 4 and 10 provides genomic loci that can demonstrate differential chromatin accessibility or transcription factor binding in cell lines deprived of estrogen. [0270] In various embodiments, without wishing to be bound by any particular scientific theory, histone methylation (e.g., H3K4me3) corresponds and/or is correlated with chromatin accessibility. In various embodiments, without wishing to be bound by any particular scientific theory, histone acetylation (e.g., H3K27ac) corresponds and/or is correlated with chromatin accessibility. In various embodiments, without wishing to be bound by any particular scientific theory, DNA methylation corresponds and/or is correlated with chromatin accessibility. [0271] In some embodiments, without wishing to be limited to any particular scientific theory, chromatin accessibility corresponds and/or is correlated with H3K4me3 modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying chromatin accessibility at one or more genomic loci in Table 1 in accordance with the section above. [0272] In some embodiments, without wishing to be limited to any particular scientific Attorney Docket No: 2014191-0041 theory, chromatin accessibility corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying chromatin accessibility at one or more genomic loci in Table 2 in accordance with the section above. [0273] In some embodiments, without wishing to be limited to any particular scientific theory, chromatin accessibility corresponds and/or is correlated with H3K4me3 modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying chromatin accessibility at one or more genomic loci in Table 3 in accordance with the section above. [0274] In some embodiments, without wishing to be limited to any particular scientific theory, chromatin accessibility corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying chromatin accessibility at one or more genomic loci in Table 5 in accordance with the section above. [0275] In some embodiments, without wishing to be limited to any particular scientific theory, chromatin accessibility corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying chromatin accessibility at one or more genomic loci in Table 6 in accordance with the section above. [0276] In some embodiments, without wishing to be limited to any particular scientific theory, chromatin accessibility corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying chromatin accessibility at one or more genomic loci in Table 9 in accordance with the section above. [0277] In some embodiments, without wishing to be limited to any particular scientific theory, chromatin accessibility corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying chromatin accessibility at one or more genomic loci in Table 10 in accordance with the section above. [0278] In various embodiments, without wishing to be bound by any particular scientific theory, histone methylation (e.g., H3K4me3) corresponds and/or is correlated with transcription Attorney Docket No: 2014191-0041 factor binding. In various embodiments, without wishing to be bound by any particular scientific theory, histone acetylation (e.g., H3K27ac) corresponds and/or is correlated with transcription factor binding. In various embodiments, without wishing to be bound by any particular scientific theory, DNA methylation corresponds and/or is correlated with transcription factor binding. [0279] In some embodiments, without wishing to be limited to any particular scientific theory, binding of RNA pol II corresponds and/or is correlated with H3K4me3 modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying binding of RNA pol II at one or more genomic loci in Table 1 in accordance with the section above. [0280] In some embodiments, without wishing to be limited to any particular scientific theory, binding of p300, mediator complex, cohesin complex or RNA pol II corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying binding of p300, mediator complex, cohesin complex or RNA pol II at one or more genomic loci in Table 2 in accordance with the section above. [0281] In some embodiments, without wishing to be limited to any particular scientific theory, binding of p300, mediator complex, cohesin complex or RNA pol II corresponds and/or is correlated with H3K4me3 modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying binding of p300, mediator complex, cohesin complex or RNA pol II corresponds at one or more genomic loci in Table 3 in accordance with the section above. [0282] In some embodiments, without wishing to be limited to any particular scientific theory, binding of p300, mediator complex, cohesin complex or RNA pol II corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying binding of p300, mediator complex, cohesin complex or RNA pol II at one or more genomic loci in Table 5 in accordance with the section above. [0283] In some embodiments, without wishing to be limited to any particular scientific theory, binding of p300, mediator complex, cohesin complex or RNA pol II corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying binding of p300, mediator complex, Attorney Docket No: 2014191-0041 cohesin complex or RNA pol II at one or more genomic loci in Table 6 in accordance with the section above. [0284] In some embodiments, without wishing to be limited to any particular scientific theory, binding of p300, mediator complex, cohesin complex or RNA pol II corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying binding of p300, mediator complex, cohesin complex or RNA pol II at one or more genomic loci in Table 9 in accordance with the section above. [0285] In some embodiments, without wishing to be limited to any particular scientific theory, binding of p300, mediator complex, cohesin complex or RNA pol II corresponds and/or is correlated with H3K27ac modifications. As a result, in some embodiments, ER pathway activity may be determined by detecting and quantifying binding of p300, mediator complex, cohesin complex or RNA pol II at one or more genomic loci in Table 10 in accordance with the section above. [0286] In some embodiments, without wishing to be limited to any particular scientific theory, binding of FOXA1, ESR1, PR, MYC, EN1, FOXM1, KLF4, AP-2, RARa, or RUNX1 corresponds and/or is correlated with histone methylation (e.g., H3K4me3), histone acetylation (e.g., H3K27ac) or DNA methylation. As a result, in some embodiments, ER activity may be determined by detecting and quantifying binding of FOXA1, ESR1, PR, MYC, EN1, FOXM1, KLF4, AP-2, RARa, RUNX1 at one or more genomic loci in Table 1 or 2 in accordance with the sections above discussing exemplary genomic loci with differential histone methylation (e.g., H3K4me3) or histone acetylation (e.g., H3K27ac). Applications [0287] Methods, kits and systems of the present disclosure include analysis of differentially modified and/or differentially accessible genomic loci to determine the ER activity of a cancer. Methods, kits and systems of the present disclosure can be used in any of a variety of applications. For example, methods, kits and systems of the present disclosure can be used in detecting and/or treating cancers based on ER activity. Methods, kits and systems of the present disclosure can also be used to detect or determine resistance of a cancer, e.g., breast, ovarian, or Attorney Docket No: 2014191-0041 endometrial cancer to a therapy or transformation from one cancer subtype to another. [0288] In various embodiments, methods, kits and systems of the present disclosure can be applied to an asymptomatic human subject. As used herein, a subject can be referred to as “asymptomatic” if the subject does not report, and/or demonstrate by non-invasively observable indicia (e.g., without one, several, or all of device-based probing, tissue sample analysis, bodily fluid analysis, surgery, or cancer screening), sufficient characteristics of cancer to support a medically reasonable suspicion that the subject is likely suffering from cancer, e.g., breast, ovarian, or endometrial cancer. Detection of early-stage cancer can be achieved using methods, kits and systems of the present disclosure, with attendant medical benefits including potential for early treatment and attendant improvement in therapeutic outcomes. [0289] In various embodiments, methods, kits and systems of the present disclosure can be applied to a symptomatic human subject. As used herein, a subject can be referred to as “symptomatic” if the subject reports, and/or demonstrates by non-invasively observable indicia (e.g., without one, several, or all of device-based probing, tissue sample analysis, bodily fluid analysis, surgery, or cancer screening), sufficient characteristics of cancer to support a medically reasonable suspicion that the subject is likely suffering from cancer, e.g., breast, ovarian, or endometrial cancer. For example, in various embodiments a sample from a subject, optionally where the subject has a cancer that is of unknown ER activity, can be assayed according to one or more embodiments of the present disclosure to determine ER activity of the cancer. In various embodiments a sample from a subject, where the subject has a cancer that is known or suspected of being ER-positive (or ER-negative), can be assayed according to one or more embodiments of the present disclosure to determine if the cancer is in fact ER-positive (or ER- negative). [0290] In some embodiments, methods, kits and systems of the present disclosure can be used to determine that a subject has an ER-positive cancer, optionally an ER-positive cancer that correlates with an ER+ Allred score of 3, 4, 5, 6, 7 or 8 based on IHC testing. In some embodiments, methods, kits and systems of the present disclosure can be used to determine that a subject has an ER-positive cancer, optionally an ER-positive cancer that correlates with an ER+ Allred score of at least 3, at least 4, at least 5, at least 6, at least 7 or 8 based on IHC testing. In some embodiments, methods, kits and systems of the present disclosure can be used to determine that a subject has an ER-negative cancer, optionally an ER-negative cancer that correlates with Attorney Docket No: 2014191-0041 ER- Allred score of 0, 1, or 2 based on IHC testing. [0291] In some embodiments, methods, kits and systems of the present disclosure can be used to validate or confirm a prior determination that a subject has an ER-positive cancer, optionally an ER-positive cancer that correlates with an ER+ Allred score of 3, 4, 5, 6, 7 or 8 based on IHC testing. In some embodiments, methods, kits and systems of the present disclosure can be used to validate or confirm a prior determination that a subject has an ER-positive cancer, optionally an ER-positive cancer that correlates with an ER+ Allred score of at least 3, at least 4, at least 5, at least 6, at least 7 or 8 based on IHC testing. In some embodiments, methods, kits and systems of the present disclosure can be used to validate or confirm a prior determination that a subject has an ER-negative cancer, optionally an ER-negative cancer that correlates with ER- Allred score of 0, 1, or 2 based on IHC testing. [0292] In some embodiments, methods, kits and systems of the present disclosure are used to identify and detect new ER related categories that are independent of IHC or ISH scoring. For example, methods provided herein can be used to identify subjects that are likely to respond to a particular ER-targeted agent and/or likely to continue to respond to a particular ER- targeted agent. It is therefore to be understood that the term “ER status” as used herein is not limited to ER-positive and ER-negative or the traditional ER scoring based on IHC or ISH testing but can encompass any ER related categories including whether a subject will or will not respond to a particular ER-targeted agent. [0293] Those of skill in the art will appreciate that regular, preventative, and/or prophylactic screening to determine ER activity improves diagnosis of cancer, including and/or particularly early-stage cancer. Thus, the present disclosure provides, among other things, methods, kits and systems particularly useful for the diagnosis and treatment of early-stage cancer. Generally, and particularly in embodiments in which ER activity determination in accordance with the present disclosure is carried out annually, and/or in which a subject is asymptomatic at time of detecting, methods, kits and systems of the present disclosure are especially likely to detect early-stage ER-positive cancer. In various embodiments, detecting in accordance with methods, kits and systems of the present disclosure reduces cancer mortality, e.g., by early cancer diagnosis. [0294] In various embodiments ER activity determination in accordance with the present disclosure is performed once for a given subject or multiple times for a given subject. In various Attorney Docket No: 2014191-0041 embodiments, ER activity determination in accordance with the present disclosure is performed on a regular basis, e.g., every six months, annually, every two years, every three years, every four years, every five years, or every ten years. [0295] In various embodiments, methods, kits and systems disclosed herein provide a determination of ER activity. In other instances, methods, kits and systems disclosed herein will be indicative of ER activity but not definitive for ER activity. In various instances in which methods, kits and systems of the present disclosure are used to determine ER activity, the same can be followed by a further confirmatory assay, which further assay can confirm, support, undermine, or reject a determination resulting from a prior determination, e.g., a determination in accordance with the present disclosure. As used herein, a confirmatory assay can be an ER test that is currently recognized by medical practitioners, e.g., ER scoring based on IHC or ISH testing. [0296] In various embodiments, methods, kits and systems disclosed herein provide a determination of ER activity in a subject for whom ER status has been determined. In some embodiments, ER status is determined after ER activity has been determined using a method, kit, and/or system disclosed herein. In some embodiments, ER status is determined contemporaneously a determination of ER activity using a method, kit, and/or system disclosed herein. Determining ER activity and ER status in combination can be useful, e.g., for determining whether a reduction in ER activity is due to a loss of ER expression (i.e., conversion from an ER+ status to an ER- status) or a downstream adaptation. In some embodiments, ER status can be determined using tissue-based assay (e.g., as described herein). In some embodiments, ER status can be determined using one or more assays that use a liquid biopsy sample (e.g., the same sample used to determine ER activity). In some embodiments, ER status can be determined using an assay that uses measurements of one or more epigenetic modifications, e.g., as described in WO2025/081094, the contents of which are incorporated by referenced herein in their entirety. [0297] In various embodiments, ER activity determination according to one or more methods, kits and/or systems disclosed herein is followed by treatment of cancer. In various embodiments, treatment of cancer includes administration of a therapeutic regimen including one or more cancer therapies provided herein, including without limitation one or more of ER targeted therapy, surgery, radiation, endocrine therapy, chemotherapy, and/or immunotherapy. Attorney Docket No: 2014191-0041 In various embodiments, treatment of cancer includes administration of a therapeutic regimen including one or more treatments provided herein as available, appropriate, and/or preferred for a particular ER activity. [0298] In various embodiments, methods, kits and systems can be used to determine whether a particular subject and/or cancer is likely to be and/or is characterized as responsive to ER targeted therapy. In some such embodiments, methods, kits and systems can be followed by treatment of the subject with an ER targeted therapy. [0299] In various embodiments, methods, kits and systems can be used to determine whether a particular subject and/or cancer is likely to be and/or is characterized as resistant to, non-responsive to, or not recommended treatment with to ER targeted therapy. In some such embodiments, methods, kits and systems can be followed by treatment with one or more of surgery and/or radiation, a HER2-targeted agent (if HER2-positive), chemotherapy and immunotherapy instead of ER targeted therapy. [0300] Responsiveness can refer to the ability or likelihood of a therapy to cause a reduction in tumor size or inhibit tumor growth or metastasis. Responsiveness can refer to improvement in prognosis (e.g., increased time to cancer recurrence or increased life expectancy, e.g., overall survival, recurrence-free survival, metastasis-free survival, or disease-free survival). Responsiveness can refer to achievement of a treatment benefit, including e.g., improvement in one or more symptoms of cancer, e.g., breast, ovarian, or endometrial cancer. Responsiveness can be measured quantitatively (e.g., as in the case of tumor size; as in the case of measurement of histone modification, chromatin accessibility, transcription factor binding, or DNA methylation at one or more genomic loci; or as in the calculation of clinical benefit (CBR)), or qualitatively (e.g., by measures such as “pathological complete response” (pCR), “clinical complete remission” (cCR), “clinical partial remission” (cPR), “clinical stable disease” (cSD), “clinical progressive disease” (cPD), or other qualitative criteria). Resistance can refer to the inability or unlikelihood of a therapy to achieve a desired therapeutic effect (e.g., a reduction in tumor size, improvement in prognosis, or other treatment benefit such as, e.g., improvement in one or more symptoms of cancer) in a subject and/or cancer. Resistance includes both acquired and natural resistance. In certain embodiments, resistance includes the extent to which one or more desired therapeutic benefits results from administration of a therapy to a subject and/or cancer is less than that expected and/or achieved in a reference (e.g., less than 90%, 80%, 70%, Attorney Docket No: 2014191-0041 60%, 50%, 40%, 30%, 20%, or 10% of benefit achieved in a reference). [0301] In various embodiments, methods, kits and systems can be used to detect the clinical efficacy of a course of therapy for cancer, e.g., breast, ovarian, or endometrial cancer. For example, methods and/or compositions of the present disclosure could be used to determine ER activity of a cancer in a subject over the course of treatment. Methods and/or compositions of the present disclosure could be used in conjunction with, or confirmed by, other means of determining ER status and/or ER activity of a cancer including, for example measurements of tumor size or character by techniques such as CT, PET, mammogram, ultrasound, palpation, histology, caliper measurement after biopsy or surgical resection, or by various qualitative, quantitative, or semi quantitative scoring systems including without limitation based on IHC or ISH testing, residual cancer burden (Symmans et al., J Clin Oncol (2007) 25:4414-4422, incorporated by reference herein in its entirety) or Miller-Payne score (Ogston et al., Breast (2003) 12:320-327, incorporated by reference herein in its entirety) in a qualitative fashion like “pathological complete response” (pCR), “clinical complete remission” (cCR), “clinical partial remission” (cPR), “clinical stable disease” (cSD), or “clinical progressive disease” (cPD). [0302] In some embodiments, methods, kits and systems for ER activity determination provided herein can inform treatment and/or payment (e.g., reimbursement for or reduction of cost of medical care, such as detecting or treatment) decisions and/or actions, e.g., by individuals, healthcare facilities, healthcare practitioners, health insurance providers, governmental bodies, or other parties interested in healthcare cost. [0303] In some embodiments, methods, kits and systems for ER activity determination provided herein can inform decision making relating to whether health insurance providers reimburse a healthcare cost payer or recipient (or not), e.g., for (1) ER activity determination itself (e.g., reimbursement for detecting otherwise unavailable, available only for periodic/regular detecting, or available only for temporally- and/or incidentally- motivated detecting); and/or for (2) treatment, including initiating, maintaining, and/or altering therapy, e.g., based on the determined ER activity. For example, in some embodiments, methods, kits and systems for ER activity determination provided herein are used as the basis for, to contribute to, or support a determination as to whether a reimbursement or cost reduction will be provided to a healthcare cost payer or recipient. In some instances, a party seeking reimbursement or cost reduction can provide results of ER activity determination conducted in accordance with the Attorney Docket No: 2014191-0041 present disclosure together with a request for such reimbursement or reduction of a healthcare cost. In some instances, a party making a determination as to whether or not to provide a reimbursement or reduction of a healthcare cost will reach a determination based in whole or in part upon receipt and/or review of results of ER activity determination conducted in accordance with the present disclosure. [0304] In various embodiments, ER activity determination using methods, kits and systems disclosed herein can be used in classifying subjects, samples, and/or tumors (e.g., breast cancer subjects, samples, and/or tumors). In various embodiments, methods, kits and systems disclosed herein can be used to generate a set of subjects, samples, and/or tumors identified according to the present methods, kits and systems each classified as comprising a particular ER activity, or having an ER activity that falls within a certain range, and optionally using two or more of such classified subjects, samples, and/or tumors to identify biomarkers that distinguish the classes (i.e., distinguish the subjects, samples, and/or tumors according to their class, e.g., according to their ER activity). [0305] For illustration purposes and without limitation, in an exemplary assay of the present disclosure, samples obtained from a subject (e.g., a liquid biopsy sample including cfDNA, e.g., a plasma sample including cfDNA) are analyzed by ChIP-seq for a histone modification (e.g., H3K4me3 and/or H3K27ac). ChIP-seq sequence reads are aligned to human genome build hg19, e.g., using the Burrows-Wheeler Aligner (BWA). Non-uniquely mapping and redundant reads are optionally discarded. To provide one example of peak calling, MACS v2.1.1.20140616 can be used for ChIP-seq peak calling with a q-value (FDR) threshold of 0.01. ChIP-seq data quality can optionally be evaluated by any of one or more of a variety of measures, including total peak number, FRiP (fraction of reads in peak) score, number of high- confidence peaks (e.g., enriched > ten-fold over background), and percent of peak overlap with “blacklist” DHS peaks derived from the ENCODE project (Amemiya et al., Sci Rep (2019) 9(1):9354). If the ChIP-seq data quality is below a particular threshold the data may be discarded and the assay repeated. ChIP-seq peaks that overlap with selected genomic loci that are differentially modified as provided herein for the relevant histone modification (Tables 1-6, 9, and 10) can then be used to determine ER activity. The number of reads overlapping the selected genomic loci for the relevant histone modification are summed, e.g., in some embodiments all the genomic loci that are differentially modified with an absolute log2(fold- Attorney Docket No: 2014191-0041 . In some embodiments, the average number of reads in the local background of each ChIP-seq peak is subtracted to improve signal to noise. The data is then log2-transformed and quantile normalized to match the distribution of the data used to train the classifier. The normalized data is then used as input into a classifier that was trained using the same histone modification and selected genomic loci. The classifier then uses the inputted data to determine ER activity of the subject’s cancer. It will be appreciated that this or similar approaches can be applied to assays of the present disclosure that quantify chromatin accessibility, transcription factor binding and/or DNA methylation. [0306] For the avoidance of any doubt, those of skill in the art will appreciate from the present disclosure that methods, kits and systems for ER activity determination of the present disclosure are at least for in vitro use. Accordingly, all aspects and embodiments of the present disclosure can be performed and/or used at least in vitro. [0307] Those of skill in the art will also appreciate that, in certain embodiments, methods of the present disclosure can be implemented on and/or in conjunction with a computer program and computer system. In some embodiments, methods of the present disclosure can be implemented on and/or in conjunction with a non-transitory computer readable storage medium encoded with the computer program, wherein the program comprises instructions that when executed by one or more processors cause the one or more processors to perform operations to perform the method. A computer system can also store and manipulate data generated by methods of the present disclosure that comprise a plurality of genomic locus modification status and/or accessibility status changes/profiles, which data can be used by a computer system in implementing methods disclosed herein. In certain embodiments, a computer system (i) receives modification status and/or accessibility status data; (ii) stores the data; and (iii) compares the data in any number of ways described herein (e.g., analysis relative to appropriate references), e.g., to determine ER activity. In certain embodiments, a computer system (i) compares the genomic locus modification and/or accessibility status to a reference; and (ii) outputs an indication of whether the modification status and/or accessibility status of the genomic locus is significantly different from the reference and/or provides a determination regarding ER activity. [0308] Numerous types of computer systems can be used to implement methods of the present disclosure according to knowledge possessed by a skilled artisan in the bioinformatics and/or computer arts. Several software components can be loaded into memory during operation Attorney Docket No: 2014191-0041 of such a computer system. The software components can comprise both software components that are standard in the art and components that are special to the present disclosure (e.g., dCHIP software described in Lin et al., Bioinformatics (2004) 20:1233-1240, incorporated herein by reference in its entirety; radial basis machine learning algorithms (RBM) known in the art). Methods of the present disclosure can also be programmed or modeled in mathematical software packages that allow symbolic entry of equations and high-level specification of processing, including specific algorithms to be used, thereby freeing a user of the need to procedurally program individual equations and algorithms. Such packages include, e.g., Matlab from Mathworks (Natick, MA), Mathematica from Wolfram Research (Champaign, IL), S-Plus from MathSoft (Seattle, WA), R from R Foundation for Statistical Computing (Vienna, Austria), Python from Python Software Foundation (Wilmington, DE), or Perl from Perl Foundation (Holland, MI). In certain embodiments, a computer system comprises a database for storage of genomic locus modification status and/or accessibility status data. Such stored profiles can be accessed and used to perform comparisons of interest at a later point in time. In addition to the exemplary program structures and computer systems described herein, other, alternative program structures and computer systems will be readily apparent to the skilled artisan. [0309] As demonstrated in the Examples, various algorithms can be applied to the comparison, between samples and references, of the modification status and/or accessibility status of genomic loci that are differentially modified in different ER states. In various embodiments, an algorithm can be a single learning statistical classifier system. Other suitable statistical algorithms are well known to those of skill in the art. For example, learning statistical classifier systems include a machine learning algorithmic technique capable of adapting to complex datasets (e.g., a panel of genomic loci of interest) and making decisions based upon such datasets. In some embodiments, a single learning statistical classifier system such as a classification tree (e.g., random forest) is used. In other embodiments, a combination of 2, 3, 4, 5, 6, 7, 8, 9, 10, or more learning statistical classifier systems are used, preferably in tandem. Examples of learning statistical classifier systems include, but are not limited to, those described in the Examples and also those using inductive learning (e.g., decision/classification trees such as random forests, classification and regression trees (C&RT), boosted trees, etc.), Probably Approximately Correct (PAC) learning, connectionist learning (e.g., neural networks (NN), artificial neural networks (ANN), neuro fuzzy networks (NFN), network structures, perceptrons Attorney Docket No: 2014191-0041 such as multi-layer perceptrons, multi-layer feed-forward networks, applications of neural networks, Bayesian learning in belief networks, etc.), reinforcement learning (e.g., passive learning in a known environment such as naive learning, adaptive dynamic learning, and temporal difference learning, passive learning in an unknown environment, active learning in an unknown environment, learning action-value functions, applications of reinforcement learning, etc.), and genetic algorithms and evolutionary programming. Other learning statistical classifier systems include support vector machines (e.g., Kernel methods), multivariate adaptive regression splines (MARS), Levenberg-Marquardt algorithms, Gauss-Newton algorithms, mixtures of Gaussians, gradient descent algorithms, and learning vector quantization (LVQ). In certain embodiments, methods of the present disclosure can include sending classification results to a medical practitioner, e.g., an oncologist. Formulation and Administration of Therapeutic Agents [0310] The present disclosure includes methods where a therapeutic agent or regimen is administered to a subject based on the ER activity of a cancer (e.g., breast cancer, ovarian cancer, or endometrial cancer). In general, the therapeutic agent or regimen provided herein will be available, appropriate, and/or preferred for the determined ER activity. Those of skill in the art will be aware of recommended and/or governmentally approved formulations and/or dosages for various therapeutic agents provided herein. [0311] The present disclosure includes pharmaceutical compositions for delivery of one or more therapeutic agents to a subject. As disclosed herein, a pharmaceutical composition may be in any form known in the art, including formulations for administration according to any route known in the art. A suitable means of administration can be selected based on the age and condition of a subject. [0312] Pharmaceutical composition forms of the present disclosure can include, e.g., liquid, semi-solid and solid dosage forms. Pharmaceutical composition forms of the present disclosure can include, e.g., liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, and liposomes. Selection or use of any particular form may depend, in part, on the intended mode of administration and therapeutic application. Accordingly, the compositions can be formulated for administration by a parenteral mode (e.g., intravenous, subcutaneous, intraperitoneal, or intramuscular injection) or a non-parenteral mode. Attorney Docket No: 2014191-0041 As used herein, parenteral administration refers to modes of administration other than enteral and topical administration, usually by injection or infusion. [0313] In some embodiments, the compositions provided herein are present in unit dosage form, which unit dosage form can be suitable for self-administration. Such a unit dosage form may be provided within a container, e.g., a pill, vial, cartridge, prefilled syringe, or disposable pen. [0314] A pharmaceutical composition of the present disclosure can be in an injectable or infusible form. For example, the present disclosure includes sterile formulations for injection or infusion, which can be formulated in accordance with conventional pharmaceutical practices. Sterile solutions can be prepared by incorporating a composition described herein in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filter sterilization. Solutions can be formulated, e.g., using distilled water, physiological saline, or an isotonic solution containing glucose and other supplements such as D- sorbitol, D-mannose, D-mannitol, or sodium chloride as an aqueous solution for injection, optionally in combination with a suitable solubilizing agent, for example, an alcohol such as ethanol and/or a polyalcohol such as propylene glycol or polyethylene glycol, and/or a nonionic surfactant such as polysorbate 80™ or HCO-50, and the like. In the case of sterile powders for the preparation of sterile injectable solutions, methods for preparation include vacuum drying and freeze-drying that yield a powder of a composition described herein plus any additional desired ingredient (see below) from a previously sterile-filtered solution thereof. The proper fluidity of a solution can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prolonged absorption of injectable compositions can be brought about by including in the composition a reagent that delays absorption, for example, monostearate salts, and gelatin. In particular instances, a pharmaceutical composition can be formulated, for example, as a buffered solution at a suitable concentration and suitable for storage, e.g., at 2-8°C (e.g., 4°C). [0315] In various embodiments, a pharmaceutical composition of the present disclosure can be formulated as a solution, microemulsion, dispersion, liposome, or other ordered structure suitable for stable storage at high concentration. Generally, dispersions are prepared by incorporating a composition described herein into a sterile vehicle that contains a basic Attorney Docket No: 2014191-0041 dispersion medium and the required other ingredients from those enumerated above. [0316] In various instances, a pharmaceutical composition can be formulated to include a pharmaceutically acceptable carrier or excipient. Examples of pharmaceutically acceptable carriers include, without limitation, any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. [0317] In certain embodiments, compositions can be formulated with a carrier that will protect the therapeutic agent against rapid release, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Many methods for the preparation of such formulations are known in the art. See, e.g., J. R. Robinson (1978) “Sustained and Controlled Release Drug Delivery Systems,” Marcel Dekker, Inc., New York. [0318] Route of administration can be parenteral, for example, administration by injection. Administration by injection can be by intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous injection. Administration can be systemic or local. In certain embodiments, a composition described herein can be therapeutically delivered to a subject by way of local administration. As used herein, “local administration” or “local delivery,” can refer to delivery that does not rely upon transport of the composition or therapeutic agent to its intended target tissue or site via the vascular system. For example, the composition may be delivered by injection or implantation of the composition or therapeutic agent or by injection or implantation of a device containing the composition or therapeutic agent. In certain embodiments, following local administration in the vicinity of a target tissue or site, the composition or therapeutic agent, or one or more components thereof, may diffuse to an intended target tissue or site that is not the site of administration. [0319] A pharmaceutical composition can be administered parenterally in the form of an injectable formulation comprising a sterile solution or suspension in water or another pharmaceutically acceptable liquid. For example, a pharmaceutical composition can be formulated by suitably combining the therapeutic molecule with pharmaceutically acceptable vehicles or media, such as sterile water and physiological saline, vegetable oil, emulsifier, suspension agent, surfactant, stabilizer, flavoring excipient, diluent, vehicle, preservative, binder, Attorney Docket No: 2014191-0041 followed by mixing in a unit dose form required for generally accepted pharmaceutical practices. Examples of oily liquid include sesame oil and soybean oil, and it may be combined with benzyl benzoate or benzyl alcohol as a solubilizing agent. Other items that may be included are a buffer such as a phosphate buffer, or sodium acetate buffer, a soothing agent such as procaine hydrochloride, a stabilizer such as benzyl alcohol or phenol, and an antioxidant. The formulated injection can be packaged in a suitable ampule. [0320] In various embodiments, subcutaneous administration can be accomplished by means of a device, such as a syringe, a prefilled syringe, an auto-injector (e.g., disposable or reusable), a pen injector, a patch injector, a wearable injector, an ambulatory syringe infusion pump with subcutaneous infusion sets, or other device for combining with a therapeutic agent for subcutaneous injection. [0321] An injection system of the present disclosure may employ a delivery pen as described in U.S. Pat. No.5,308,341. Pen devices, most commonly used for self-delivery of insulin to patients with diabetes, are well known in the art. Such devices can include at least one injection needle, are typically pre-filled with one or more therapeutic unit doses of a solution that includes the therapeutic agent and are useful for rapidly delivering solution to a subject with as little pain as possible. One medication delivery pen includes a vial holder into which a vial of a therapeutic or other medication may be received. The pen may be an entirely mechanical device or it may be combined with electronic circuitry to accurately set and/or indicate the dosage of medication that is injected into the user. See, e.g., U.S. Pat. No.6,192,891. In some embodiments, the needle of the pen device is disposable and the kits include one or more disposable replacement needles. Pen devices suitable for delivery of any one of the presently featured compositions are also described in, e.g., U.S. Pat. Nos.6,277,099; 6,200,296; and 6,146,361, the disclosures of each of which are incorporated herein by reference in their entirety. A microneedle-based pen device is described in, e.g., U.S. Pat. No.7,556,615, the disclosure of which is incorporated herein by reference in its entirety. See also the Precision Pen Injector (PPI) device, MOLLY^TM, manufactured by Scandinavian Health Ltd. [0322] In certain embodiments, administration of a therapeutic agent as described herein is achieved by administering to a subject a nucleic acid encoding a therapeutic agent described herein. Nucleic acids encoding a therapeutic agent described herein can be incorporated into a gene construct to be used as a part of a gene therapy protocol to deliver nucleic acids that can be Attorney Docket No: 2014191-0041 used to express and produce therapeutic agent within cells. Expression constructs of such components may be administered in any therapeutically effective carrier, e.g., any formulation or composition capable of effectively delivering the component gene to cells in vivo. Approaches include insertion of the subject gene in viral vectors including recombinant retroviruses, adenovirus, adeno-associated virus, lentivirus, and herpes simplex virus-1 (HSV-1), or recombinant bacterial or eukaryotic plasmids. Viral vectors can transfect cells directly; plasmid DNA can be delivered with the help of, for example, cationic liposomes (lipofectin) or derivatized, polylysine conjugates, gramicidin S, artificial viral envelopes or other such intracellular carriers, as well as direct injection of the gene construct or CaPO₄ precipitation. Examples of suitable retroviruses include adenovirus-derived vectors, adeno-associated virus (AAV), pLJ, pZIP, pWE, and pEM which are known to those skilled in the art. [0323] In some embodiments, a composition can be formulated for storage at a temperature below 0°C (e.g., -20°C or -80°C). In some embodiments, the composition can be formulated for storage for up to 2 years (e.g., one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, 10 months, 11 months, 1 year, or 2 years) at 2-8°C (e.g., 4°C). Thus, in some embodiments, the compositions described herein are stable in storage for at least 1 year at 2-8°C (e.g., 4°C). [0324] A pharmaceutical composition can include a therapeutically effective amount of a therapeutic agent described herein. Such effective amounts can be readily determined by one of ordinary skill in the art. A therapeutically effective amount can be an amount at which any toxic or detrimental effects of the composition are outweighed by therapeutically beneficial effects. In some embodiments, a dose can also be chosen to reduce or avoid production of antibodies or other host immune responses against a therapeutic agent. Those of skill in the art will appreciate that data obtained from cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. In various embodiments, the amount of active ingredient included in a pharmaceutical composition is such that a suitable dose within the designated range can be administered to subjects. The dose and method of administration can vary depending on weight, age, condition, and other characteristics of a patient, and can be suitably selected as needed by those skilled in the art. [0325] Pharmaceutical compositions including certain therapeutic agents, e.g., therapeutic antibodies, can be administered as a fixed dose, or in a milligram per kilogram Attorney Docket No: 2014191-0041 (mg/kg) dose. While in no way intended to be limiting, an exemplary single dose of certain pharmaceutical compositions described herein can include certain therapeutic agents as described herein in an amount equal to, e.g., 0.001 to 1000 mg/kg, 1-1000 mg/kg, 1-100 mg/kg, 0.5-50 mg/kg, 0.1-100 mg/kg, 0.5-25 mg/kg, 1-20 mg/kg, and 1-10 mg/kg body weight. Exemplary dosages of a composition described herein include, without limitation, 0.1 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, or 20 mg/kg. The present disclosure is not limited to such ranges or dosages. [0326] The present disclosure further includes methods of preparing pharmaceutical compositions of the present disclosure and kits including pharmaceutical compositions of the present disclosure. [0327] In various embodiments, therapeutic agents of the present disclosure can be administered to a subject in a course of treatment that further includes administration of one or more additional therapeutic agents or therapies that are not therapeutic agents (e.g., surgery or radiation). Combination therapies of the present disclosure can include simultaneous exposure of a subject to therapeutic agents of two or more therapeutic regimens. [0328] In certain embodiments, a therapeutic agent as described herein can be administered together with (e.g., at the same time and/or in the same composition as) an additional agent or therapy. In certain embodiments, a therapeutic agent of the present disclosure can be administered separately from an additional therapeutic agent or therapy (e.g., at a different time and/or in a different composition than the additional therapeutic agent or therapy). Dosing regimens of a therapeutic agent and one or more additional therapeutic agents with which it is administered in combination can be coordinated or independently determined. In various embodiments, an additional therapeutic agent or therapy administered in combination with a therapeutic agent as described herein can be administered at the same time as therapeutic agent, on the same day as therapeutic agent, or in the same week as therapeutic agent. In various embodiments, an additional therapeutic agent or therapy administered in combination with a therapeutic agent as described herein can be administered such that administration of the therapeutic agent and the additional therapeutic agent or therapy are separated by one or more hours before or after, one or more days before or after, one or more weeks before or after, or one or more months before or after administration of the therapeutic agent. In various embodiments, the administration frequency and/or dosage of one or more additional therapeutic agents can be Attorney Docket No: 2014191-0041 the same as, similar to, or different from the administration frequency of a therapeutic agent. In some embodiments, the two or more regimens can be administered simultaneously; in some embodiments, such regimens can be administered sequentially (e.g., all “doses” of a first regimen are administered prior to administration of any doses of a second regimen); in some embodiments, such therapeutic agents are administered in overlapping dosing regimens. [0329] In certain embodiments, administration of a therapeutic agent can be to a subject having previously received, scheduled to receive, or in the course of a treatment regimen including an additional cancer therapy. Administration of a therapeutic agent can, in some instances, improve delivery or efficacy of another therapeutic agent or therapy with which it is administered in combination. [0330] It is contemplated that therapeutic agent combination therapies can demonstrate synergy and/or greater-than-additive effects between a therapeutic agent and one or more additional therapeutic agents with which it is administered in combination. A therapeutic agent can be administered in any effective amount as determined independently or as determined by the joint action of therapeutic agent and any of one or more additional therapeutic agents or therapies administered. Administration of the therapeutic agent may, in some embodiments, reduce the therapeutically effective dosage, required dosage, or administered dosage of the additional therapeutic agent or therapy relative to a reference regimen for administration of additional therapeutic agent or therapy or therapy absent the therapeutic agent. In certain embodiments, a composition described herein can replace or augment other previously or currently administered therapy. For example, upon treating with therapeutic agent, administration of one or more additional therapeutic agents or therapies can cease or diminish, e.g., be administered at lower levels. Kits [0331] The present disclosure includes kits for detecting modification and/or accessibility of one or more genomic loci. In some embodiments, the present disclosure provides kits for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci. Kits of the present disclosure can include, e.g., reagents such as buffers and/or antibodies useful in the detection and quantification of histone modifications. In certain embodiments, a kit of the present disclosure Attorney Docket No: 2014191-0041 can include at least one antibody that selective binds a histone modification selected from H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac, H3K4me1, H3K4me2, or H3K4me3, or pan acetylation. In certain embodiments, a kit of the present disclosure can include at least one antibody that selective binds H3K4me3 modifications. In certain embodiments, a kit of the present disclosure can include at least one antibody that selective binds H3K27ac modifications. A kit of the present disclosure can include instructional materials disclosing or describing the use of the kit in a method of determining ER activity and/or treatment disclosed herein. In various embodiments, a kit of the present disclosure can include one or more therapeutic agents useful in the treatment of cancer, e.g., as disclosed herein, optionally in combination with instruction materials for treatment of cancer, e.g., breast cancer, ovarian cancer, or endometrial cancer based on ER activity. [0332] In some embodiments, a kit of the present disclosure comprises reagents for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci, wherein the one or more genomic loci are selected from Table 1 and/or 2. [0333] In some embodiments, the kit comprises reagents for quantifying H3K4me3 for at least 5, 10, 20, 30, or 38 genomic loci in Table 1. In some embodiments, the kit comprises reagents for quantifying H3K27ac for at least 5, 10, 20, 30, 40, or 50 genomic loci in Table 2. In some embodiments, the kit comprises one or more antibodies for use in ChIP-seq, optionally wherein the one or more antibodies specifically bind H3K4me3- or H3K27ac-modified histones. [0334] In some embodiments, the kit comprises reagents for isolation of cell-free DNA (cfDNA) from a liquid biopsy sample. In some embodiments, the kit comprises reagents for library preparation for sequencing. In some embodiments, the kit comprises reagents for sequencing. In some embodiments, the kit comprises instructions for determining ER activity of a cancer in a subject. Systems [0335] The present disclosure includes systems for detecting modification and/or accessibility of one or more genomic loci. In some embodiments, the present disclosure provides systems for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci. Attorney Docket No: 2014191-0041 Systems of the present disclosure can include a sequencer configured to generate a sequencing dataset from a sample; and a non-transitory computer readable storage medium and/or a computer system. [0336] In some embodiments, the non-transitory computer readable storage medium is encoded with a computer program, wherein the program comprises instructions that when executed by one or more processors cause the one or more processors to perform operations to perform a method of the present disclosure. [0337] In some embodiments, the computer system comprises a memory and one or more processors coupled to the memory, wherein the one or more processors are configured to perform a method of the present disclosure. [0338] In some embodiments, the sequencer is configured to generate a Whole Genome Sequencing (WGS) dataset from the sample. In some embodiments, the system also includes a sample preparation device configured to prepare the sample for sequencing from a biological sample, optionally a liquid biopsy sample. The sample preparation device may include reagents for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci in cell-free DNA (cfDNA) from the biological sample, optionally the liquid biopsy sample. [0339] Systems of the present disclosure can include, e.g., reagents such as buffers and/or antibodies useful in the detection and quantification of histone modifications. In certain embodiments, a system of the present disclosure can include at least one antibody that selective binds a histone modification selected from H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac, H3K4me1, H3K4me2, or H3K4me3, or pan acetylation. In certain embodiments, a system of the present disclosure can include at least one antibody that selective binds H3K4me3 modifications. In certain embodiments, a system of the present disclosure can include at least one antibody that selective binds H3K27ac modifications. A system of the present disclosure can include instructional materials disclosing or describing the use of the system in a method of determining ER activity and/or treatment disclosed herein. [0340] In some embodiments, a system of the present disclosure comprises reagents for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci, wherein the one or Attorney Docket No: 2014191-0041 more genomic loci are selected from Tables 1 and/or 2. [0341] In some embodiments, the system comprises reagents for quantifying H3K4me3 for at least 5, 10, 20, 30, or 35 genomic loci in Table 1. In some embodiments, the system comprises reagents for quantifying H3K27ac for at least 5, 10, 20, 30, 40, or 50 genomic loci in Table 2. In some embodiments, the system comprises one or more antibodies for use in ChIP- seq, optionally wherein the one or more antibodies specifically bind H3K4me3- or H3K27ac- modified histones. [0342] In some embodiments, the system comprises reagents for isolation of cell-free DNA (cfDNA) from a liquid biopsy sample. In some embodiments, the sequencer comprises reagents for library preparation for sequencing. In some embodiments, the sequencer comprises reagents for sequencing. In some embodiments, the system comprises instructions for determining ER activity of a cancer in a subject. Definitions [0343] “A” or “An”: The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” refers to one element or more than one element. [0344] About: The term “about”, when used herein in reference to a value, refers to a value that is similar, in context, to the referenced value. In general, those skilled in the art, familiar with the context, will appreciate the relevant degree of variance encompassed by “about” in that context. For example, in some embodiments, the term “about” can encompass a range of values that within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or within a fraction of a percent, of the referenced value. [0345] “Accessibility Status” or “Chromatin Accessibility Status”: As used herein, “accessibility status” or “chromatin accessibility status” of a genomic locus refers to the frequency with which DNA sequences corresponding to the genomic locus are identified in an assay for detection of accessible chromatin. Accessibility status can be determined by various assays known in the art, including without limitation ChIP-seq as one example. Where two samples are separately analyzed by the same assay or comparable assays for detection of accessible DNA sequences, differences in chromatin accessibility status of genomic loci can be Attorney Docket No: 2014191-0041 detected. Accessibility status can be compared to a standard or reference. A sample that has an accessibility status that differs in accessibility status from a standard or reference can be referred to as differentially modified. Suitable assays for determining chromatin accessibility are known in the art. Exemplary assays include ATAC-seq (Assay of Transpose Accessible Chromatin sequencing), NOMe-seq (Nucleosome Occupancy and Methylome sequencing), FAIRE-seq (Formaldehyde-Assisted Isolation of Regulatory Elements sequencing), MNase-seq (Micrococcal Nuclease digestion with sequencing), a DNase hypersensitivity assay, and/or a fragmentomics assay. [0346] Administration: As used herein, the term “administration” typically refers to the administration of a disease appropriate (e.g., appropriate for administration to a subject having a certain ER activity) treatment. In some embodiments, the disease appropriate treatment may comprise administering a composition to a subject, for example to achieve delivery of an agent that is, is included in, or is otherwise delivered by, the composition. In some embodiments, the disease appropriate treatment may comprise administering an appropriate surgical procedure or radiological procedure, optionally in combination with administration of a composition. [0347] Agent: As used herein, the term “agent” may refer to any chemical or physical entity, including without limitation any of one or more of an atom, e.g., a radioactive atom, molecule, compound, conjugate, polypeptide, polynucleotide, polysaccharide, lipid, cell, or combination or complex thereof. [0348] Antibody: As used herein, the term “antibody” refers to a polypeptide that includes one or more canonical immunoglobulin sequence elements sufficient to confer specific binding to a particular antigen (e.g., a heavy chain variable domain, a light chain variable domain, and/or one or more CDRs). Thus, the term antibody includes, without limitation, human antibodies, non-human antibodies, synthetic and/or engineered antibodies, fragments thereof, and agents including the same. Antibodies can be naturally occurring immunoglobulins (e.g., generated by an organism reacting to an antigen). Synthetic, non-naturally occurring, or engineered antibodies can be produced by recombinant engineering, chemical synthesis, or other artificial systems or methodologies known to those of skill in the art. [0349] As is well known in the art, typical human immunoglobulins are approximately 150 kD tetrameric agents that include two identical heavy (H) chain polypeptides (about 50 kD each) and two identical light (L) chain polypeptides (about 25 kD each) that associate with each Attorney Docket No: 2014191-0041 other to form a structure commonly referred to as a “Y-shaped” structure. Typically, each heavy chain includes a heavy chain variable domain (VH) and a heavy chain constant domain (CH). The heavy chain constant domain includes three CH domains: CH1, CH2 and CH3. A short region, known as the “switch”, connects the heavy chain variable and constant regions. The “hinge” connects CH2 and CH3 domains to the rest of the immunoglobulin. Each light chain includes a light chain variable domain (VL) and a light chain constant domain (CL), separated from one another by another “switch.” Each variable domain contains three hypervariable loops known as “complement determining regions” (CDR1, CDR2, and CDR3) and four somewhat invariant “framework” regions (FR1, FR2, FR3, and FR4). In each VH and VL, the three CDRs and four FRs are arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions of a heavy and/or a light chain are typically understood to provide a binding moiety that can interact with an antigen. Constant domains can mediate binding of an antibody to various immune system cells (e.g., effector cells and/or cells that mediate cytotoxicity), receptors, and elements of the complement system. Heavy and light chains are linked to one another by a single disulfide bond, and two other disulfide bonds connect the heavy chain hinge regions to one another, so that the dimers are connected to one another and the tetramer is formed. When natural immunoglobulins fold, the FR regions form the beta sheets that provide the structural framework for the domains, and the CDR loop regions from both the heavy and light chains are brought together in three- dimensional space so that they create a single hypervariable antigen binding site located at the tip of the Y structure. [0350] In some embodiments, an antibody is a polyclonal, monoclonal, monospecific, or multispecific antibody (e.g., a bispecific antibody). In some embodiments, an antibody includes at least one light chain monomer or dimer, at least one heavy chain monomer or dimer, at least one heavy chain-light chain dimer, or a tetramer that includes two heavy chain monomers and two light chain monomers. Moreover, the term “antibody” can include (unless otherwise stated or clear from context) any art-known constructs or formats utilizing antibody structural and/or functional features including without limitation intrabodies, domain antibodies, antibody mimetics, Zybodies®, Fab fragments, Fab’ fragments, F(ab’)2 fragments, Fd’ fragments, Fd fragments, isolated CDRs or sets thereof, single chain antibodies, single-chain Fvs (scFvs), disulfide-linked Fvs (sdFv), polypeptide-Fc fusions, single domain antibodies (e.g., shark single Attorney Docket No: 2014191-0041 domain antibodies such as IgNAR or fragments thereof), cameloid antibodies, camelized antibodies, masked antibodies (e.g., Probodies®), affybodies, anti-idiotypic (anti-Id) antibodies (including, e.g., anti-anti-Id antibodies), Small Modular ImmunoPharmaceuticals (SMIPs), single chain or Tandem diabodies (TandAb®), VHHs, Anticalins®, Nanobodies®, minibodies, BiTE®s, ankyrin repeat proteins or DARPINs®, Avimers®, DARTs, TCR-like antibodies, Adnectins®, Affilins®, Trans-bodies®, Affibodies®, TrimerX®, MicroProteins, Fynomers®, Centyrins®, KALBITOR®s, chimeric antigen receptors (CARs), engineered T-cell receptors (TCRs), and antigen-binding fragments of any of the above. [0351] In various embodiments, an antibody includes one or more structural elements recognized by those skilled in the art as a complementarity determining region (CDR) or variable domain. In some embodiments, an antibody can be a covalently modified (“conjugated”) antibody (e.g., an antibody that includes a polypeptide including one or more canonical immunoglobulin sequence elements sufficient to confer specific binding to a particular antigen, where the polypeptide is covalently linked with one or more of a therapeutic agent, a detectable moiety, another polypeptide, a glycan, or a polyethylene glycol molecule). In some embodiments, antibody sequence elements are humanized, primatized, chimeric, etc., as is known in the art. [0352] An antibody including a heavy chain constant domain can be, without limitation, an antibody of any known class, including but not limited to, IgA, secretory IgA, IgG, IgE and IgM, based on heavy chain constant domain amino acid sequence (e.g. include but are not limited to human IgG1, IgG2, IgG3 and IgG4. “Isotype” refers to the Ab class or subclass (e.g., IgM or IgG1) that is encoded by the heavy chain constant region genes. As used herein, a “light chain” can be of a distinct type, e.g. the amino acid sequence of the light chain constant domain. In some embodiments, an antibody has constant region sequences that are characteristic of mouse, rabbit, primate, or human immunoglobulins. Naturally produced immunoglobulins are glycosylated, typically on the CH2 domain. As is known in the art, affinity and/or other binding attributes of Fc regions for Fc receptors can be modulated through glycosylation or other modification. In some embodiments, an antibody may lack a covalent modification (e.g., attachment of a glycan) that it would have if produced naturally. In some embodiments, antibodies produced and/or utilized in accordance Attorney Docket No: 2014191-0041 with the present invention include glycosylated Fc domains, including Fc domains with modified or engineered glycosylation. [0353] In some embodiments, an antibody can be specific for a particular histone modification (e.g., an antibody can bind one histone modification, e.g., H3K27ac with a higher affinity than other histone modifications, under conditions that are commonly used in ChIP-seq experiments). In some embodiments, an antibody is specific for an H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac, H3K4me1, H3K4me2, or H3K4me3 modification. In some embodiments, an antibody is specific for an H3K27ac modification. In some embodiments, an antibody is specific for an H3K4me3 modification. [0354] In some embodiments, an antibody is a “pan” antibody. As used herein, the term pan antibody refers to an antibody that can bind a group of histone modifications having one or more features that are similar. In some embodiments, a pan antibody is a pan-methylation antibody (e.g., an antibody that can bind a histone, e.g., H3 that comprises at least one methylated lysine, wherein the at least one methylated lysine can be at any one of a plurality of amino acid positions, e.g., in some embodiments, a pan-methylation antibody can bind an H3 protein comprising a methylated lysine at any position). In some embodiments, a pan antibody is a pan-acetylation antibody (e.g., an antibody that can bind a histone, e.g., H3 that comprises at least one acetylated lysine, wherein the at least one acetylated lysine can be at any one of a plurality of amino acid positions, e.g., a pan-acetylation antibody can bind an H3 protein comprising an acetylated lysine at any position). In some embodiments, a pan antibody can bind one or more histone modifications that are associated with transcription activation. In some embodiments, a pan antibody can bind one or more histone modifications that are associated with transcription silencing. [0355] Antibody fragment: As used herein, an “antibody fragment” refers to a portion of an antibody or antibody agent as described herein, and typically refers to a portion that includes an antigen-binding portion or variable region thereof. An antibody fragment can be produced by any means. For example, in some embodiments, an antibody fragment can be enzymatically or chemically produced by fragmentation of an intact antibody or antibody agent. Alternatively, in some embodiments, an antibody fragment can be recombinantly produced, i.e., by expression of an engineered nucleic acid sequence. In some embodiments, an antibody fragment can be wholly or partially synthetically produced. In some embodiments, an antibody fragment Attorney Docket No: 2014191-0041 (particularly an antigen-binding antibody fragment) can have a length of at least about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190 amino acids or more, in some embodiments at least about 200 amino acids. [0356] Associated with: Two events or entities are “associated” with one another, as that term is used herein, if the presence, level and/or form of one is correlated with that of the other. For example, a particular entity (e.g., an epigenetic profile comprising one or more histone modifications at a set of genomic loci, etc.) is considered to be associated with a particular disease, disorder, or condition, if its presence, level and/or form correlates with incidence of and/or susceptibility to the disease, disorder, or condition (e.g., across a relevant population). In some embodiments, two or more entities are physically “associated” with one another if they interact, directly or indirectly, so that they are and/or remain in physical proximity with one another. In some embodiments, two or more entities that are physically associated with one another are covalently linked to one another; in some embodiments, two or more entities that are physically associated with one another are not covalently linked to one another but are non- covalently associated, for example by means of hydrogen bonds, van der Waals interaction, hydrophobic interactions, magnetism, or a combination thereof. [0357] “Between” or “From”: As used herein, the term “between” refers to content that falls between indicated upper and lower, or first and second, boundaries, inclusive of the boundaries. Similarly, the term “from”, when used in the context of a range of values, indicates that the range includes content that falls between indicated upper and lower, or first and second, boundaries, inclusive of the boundaries. [0358] Biological Sample: As used herein, the term “biological sample” typically refers to a sample obtained or derived from a biological source (e.g., a tissue or organism or cell) of interest, as described herein. In some embodiments, a biological source is or includes an organism, such as a human subject. In some embodiments, a biological sample is or includes a biological tissue or fluid. In some embodiments, a biological sample can be or include cells, tissue, or bodily fluid. “Bodily fluids” refer to fluids that are excreted or secreted from the body as well as fluids that are normally not (e.g., blood, serum, plasma, Cowper’s fluid or pre- ejaculate fluid, chyle, chyme, stool, interstitial fluid, intracellular fluid, lymph, menses, saliva, sebum, semen, serum, sweat, synovial fluid, tears, urine, vitreous humor, vomit). In some embodiments, a biological sample can be or include blood, blood components, cell-free DNA Attorney Docket No: 2014191-0041 (cfDNA), circulating-tumor DNA (ctDNA), ascites, biopsy samples, surgical specimens, cell- containing body fluids, sputum, saliva, feces, urine, cerebrospinal fluid, peritoneal fluid, pleural fluid, lymph, gynecological fluids, secretions, excretions, skin swabs, vaginal swabs, oral swabs, nasal swabs, washings or lavages such as a ductal lavages or bronchoalveolar lavages, aspirates, scrapings, or bone marrow. In some embodiments, a biological sample is a liquid biopsy sample obtained from a bodily fluid. In some embodiments, a biological sample is or includes DNA obtained from a single subject or from a plurality of subjects. A biological sample can be a “primary sample” obtained directly from a biological source or can be a “processed sample”, i.e., a sample that was derived from a primary sample, e.g., via dilution, purification, mixing with one or more reagents, or any other processing step(s) as described herein. A biological sample can also be referred to as a “sample.” [0359] Blood component: As used herein, the term “blood component” refers to any component of whole blood, including red blood cells, white blood cells, plasma, platelets, endothelial cells, mesothelial cells, epithelial cells, cell-free DNA (cfDNA), and circulating- tumor DNA (ctDNA). Blood components also include the components of plasma, including proteins, metabolites, lipids, nucleic acids, and carbohydrates, and any other cells that can be present in blood, e.g., due to pregnancy, organ transplant, infection, injury, or disease. [0360] Cancer: As used herein, the terms “cancer,” “malignancy,” “tumor,” and “carcinoma,” are used interchangeably to refer to a disease, disorder, or condition in which cells exhibit or exhibited relatively abnormal, uncontrolled, and/or autonomous growth, so that they display or displayed an abnormally elevated proliferation rate and/or aberrant growth phenotype. In some embodiments, a cancer can include one or more tumors. In some embodiments, a cancer can be or include cells that are precancerous (e.g., benign), malignant, pre-metastatic, metastatic, and/or non-metastatic. In some embodiments, a cancer can be or include a solid tumor. [0361] Examples of cancer include but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia or lymphoid malignancies. More particular examples of such cancers include, but are not limited to, breast cancer (e.g., an HR+ breast cancer (e.g., an ER+ breast cancer (e.g., luminal A breast cancer or luminal B breast cancer)), DCIS, and/or a metastatic or a locally advanced breast cancer)); lung cancer, including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung; bladder cancer (e.g., urothelial bladder cancer (UBC), muscle invasive bladder cancer (MIBC), Attorney Docket No: 2014191-0041 and BCG-refractory non-muscle invasive bladder cancer (NMIBC)); kidney or renal cancer (e.g., renal cell carcinoma (RCC)); cancer of the urinary tract; prostate cancer, such as castration- resistant prostate cancer (CRPC); cancer of the peritoneum; hepatocellular cancer; gastric or stomach cancer, including gastrointestinal cancer and gastrointestinal stromal cancer; pancreatic cancer; glioblastoma; cervical cancer; ovarian cancer; liver cancer; hepatoma; colon cancer; rectal cancer; colorectal cancer; endometrial or uterine carcinoma; salivary gland carcinoma; prostate cancer; vulval cancer; thyroid cancer; hepatic carcinoma; anal carcinoma; penile carcinoma; melanoma, including superficial spreading melanoma, lentigo maligna melanoma, acral lentiginous melanomas, and nodular melanomas; multiple myeloma and B-cell lymphoma (including low grade/follicular non-Hodgkin’s lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade/follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom’s Macroglobulinemia); chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); acute myologenous leukemia (AML); hairy cell leukemia; chronic myeloblastic leukemia (CML); post-transplant lymphoproliferative disorder (PTLD); and myelodysplastic syndromes (MDS), as well as abnormal vascular proliferation associated with phakomatoses, edema (such as that associated with brain tumors), Meigs’ syndrome, brain cancer, head and neck cancer, and associated metastases. [0362] Breast Cancer: As used herein, the term “breast cancer” refers to histologically or cytologically confirmed cancer of the breast. In some embodiments, the breast cancer is a carcinoma. In some embodiments, the breast cancer is an adenocarcinoma. In some embodiments, the breast cancer is a sarcoma. In some embodiments, the breast cancer is an HR+ breast cancer. In some embodiments, the HR+ breast cancer is an ER+ breast cancer. In some embodiments, the HR+ breast cancer is an ER- breast cancer. In some embodiments, the ER+ breast cancer is luminal A breast cancer. In some embodiments, the ER+ breast cancer is luminal B breast cancer. In some embodiments, the breast cancer is a ER+/HER2+ or ER+/HER2- breast cancer. In some embodiments, the breast cancer is a metastatic or a locally advanced breast cancer. [0363] As used herein, the term “locally advanced breast cancer” refers to cancer that has spread from where it started in the breast to nearby tissue or lymph nodes, but not to other parts Attorney Docket No: 2014191-0041 of the body. [0364] As used herein, the term “metastatic breast cancer” refers to cancer that has spread from the breast to other parts of the body, such as the bones, liver, lungs, or brain. Metastatic breast cancer may also be referred to as stage IV breast cancer. [0365] As used herein, the term “ductal carcinoma in situ breast cancer” or (DCIS cancer) refers to breast cancers characterized as being intraductal, non-evasive, and pre-invasive primary tumors as understood in the art. [0366] In some embodiments, a cancer is associated with a certain ER expression or activity status, e.g., an ER-positive breast cancer, an ER-positive breast cancer with high ER activity, etc. [0367] Combination therapy: As used herein, the term “combination therapy” refers to administration to a subject of two or more therapeutic agents or therapeutic regimens such that the two or more therapeutic agents or therapeutic regimens together treat a disease, condition, or disorder of the subject. In some embodiments, the two or more therapeutic agents or therapeutic regimens can be administered simultaneously, sequentially, or in overlapping dosing regimens. Those of skill in the art will appreciate that combination therapy includes but does not require that the two therapeutic agents or therapeutic regimens be administered together in a single composition, nor at the same time. [0368] Corresponding to: As used herein, the term “corresponding to” may be used to designate the position/identity of a structural element in a compound or composition through comparison with an appropriate reference compound or composition. For example, in some embodiments, a monomeric residue in a polymer (e.g., an amino acid residue in a polypeptide or a nucleic acid residue in a polynucleotide) may be identified as “corresponding to” a residue in an appropriate reference polymer. For example, those of skill in the art appreciate that residues in a provided polypeptide or polynucleotide sequence are often designated (e.g., numbered or labeled) according to the scheme of a related reference sequence (even if, e.g., such designation does not reflect literal numbering of the provided sequence). By way of illustration, if a reference sequence includes a particular amino acid motif at positions 100-110, and a second related sequence includes the same motif at positions 110-120, the motif positions of the second related sequence can be said to “correspond to” positions 100-110 of the reference sequence. Those of skill in the art appreciate that corresponding positions can be readily identified, e.g., by Attorney Docket No: 2014191-0041 alignment of sequences, and that such alignment is commonly accomplished by any of a variety of known tools, strategies, and/or algorithms, including without limitation software programs such as, for example, BLAST, CS-BLAST, CUDASW++, DIAMOND, FASTA, GGSEARCH/GLSEARCH, Genoogle, HMMER, HHpred/HHsearch, IDF, Infernal, KLAST, USEARCH, parasail, PSI-BLAST, PSI-Search, ScalaBLAST, Sequilab, SAM, SSEARCH, SWAPHI, SWAPHI-LS, SWIMM, or SWIPE. Two sequences can be identified as corresponding if they are identical or if they share substantial identity, e.g., at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, e.g., over a length of at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500 or more residues. In various embodiments, a nucleic acid sequence can correspond to a sequence that is identical or substantially identical (e.g., at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical) to the complement of the nucleic acid sequence, e.g., over a length of at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500 or more nucleic acid residues. [0369] “Diagnosing”, “Detecting”, “Determining” or “Screening for”: As used herein, “diagnosing”, “detecting”, “determining”, “screening for” the presence of a condition or disease (e.g., ER-positive cancer), or a related state (e.g., responsiveness of an ER-positive cancer to one or more ER-targeted therapies) includes the act, process, and/or outcome of determining whether, and/or the qualitative of quantitative probability that, a subject has or will develop the condition, disease, or related state. In some instances, diagnosing can include a determination relating to prognosis and/or likely response to one or more general or particular therapeutic agents or regimens. [0370] Differentially accessible: As used herein, the term “differentially accessible” describes a genomic locus for which chromatin accessibility status differs between a first condition or sample and a second condition or sample (e.g., a standard or reference). A differentially accessible genomic locus can include a greater or smaller measured accessibility under a selected condition of interest, such as activation of the ER signaling pathway, as compared to a reference state, such as a system in which the ER signaling pathway has not been activated. [0371] Differentially modified: As used herein, the term “differentially modified” describes a genomic locus for which histone modification status and/or DNA methylation status differs between a first condition or sample and a second condition or sample (e.g., a standard or Attorney Docket No: 2014191-0041 reference). A differentially modified genomic locus can include a greater or smaller number or frequency of histone modification and/or DNA methylations under a selected condition of interest, such as activated ER signaling, as compared to a reference state, such as ER-negative state or a state in which the ER signaling pathway has not been stimulated. [0372] Enhancer signal: As used herein, the term “enhancer signal” refers to an epigenetic modification or chromatin state in an enhancer region that is associated with increased expression of a gene regulated by the enhancer region. Examples of such enhancer signals are known in the art and include, e.g., histone modifications (e.g., histone acetylation (e.g., H3K27ac) and/or H3K4me1), histone variants (e.g., H2A.Z), coactivators (e.g., EP300, CREBBP, and/or Mediator), chromatin accessibility (e.g., as measured using a method described herein), and/or transcription factor binding (e.g., ER binding). In some embodiments, enhancer signal can be measured by quantifying histone acetylation (e.g., H3K27ac), chromatin accessibility, and/or transcription factor binding (e.g., ER binding). As used herein, “enhancer” and “enhancer region,” are used interchangeably. [0373] ER dependence: As used herein, the term “ER dependence” refers to the degree to which a cancer is dependent on ER signaling activity for continued growth and is a measure of ER pathway activity that is induced by ER activation. In some embodiments, ER dependence can be assessed by adjusting for one or more mechanisms of resistance to an ER-targeted agent (e.g., tamoxifen), and/or not quantifying signal of one or more epigenetic modifications at a loci that is proximal (e.g., within 2 kB of) one or more regions of the genome that is associated with resistance to an ER-targeted agent (e.g., not quantifying one or more epigenetic modifications at a genomic loci that is proximal to a FOXA1 locus and/or not quantifying one or more epigenetic modifications at a genomic loci that is proximal to a region that exhibits an increase of one or more epigenetic modifications associated when cells are deprived of estrogen) [0374] Among other points of differentiation, in some embodiments, methods provided herein differ from methods for measuring ER activity that have previously been developed in that they can be adjusted for ER-targeted agent resistance mechanisms. In some embodiments, this adjustment is achieved by incorporating features that do not correlate with or that anti- correlate with known ER-targeted agent resistance mechanisms. In some embodiments, features that do not correlate with or that anti-correlate with known ER-targeted agent resistance mechanisms are selected by use of genomic loci that (i) are associated with (e.g., within 2,000 bp Attorney Docket No: 2014191-0041 of) an ER binding site, and/or (ii) are associated with (e.g., within 200,000 bp) of a gene that is repressed in cancer exhibiting resistance to ER-targeting agents (e.g., tamoxifen), and (iii) optionally that are not associated with (e.g., within 2,000 bp of) a FOXA1 binding site associated with resistance to an ER-targeting agent (e.g., tamoxifen). In some embodiments, methods adjust for (e.g., subtract) measures of epigenetic modifications (e.g., promoter signal and/or enhancer signal) at one or more genomic loci that (i) can exhibit increased promoter signal or enhancer signal in cell lines deprived of estrogen, and/or (ii) are associated with (e.g., within 2,000 bp) a genomic locus associated with resistance to an ER-targeted agent (e.g., within 2,000 bp of a FOXA1 binding site associated with tamoxifen resistance). [0375] As used herein, an “ER dependence index” or an “ER dependence index score” refers to a measure of ER dependence. [0376] Epigenetic modification: As used herein, the term “epigenetic modification” refers to a heritable alteration to the genome that is not due to changes in DNA sequence. Epigenetic modifications include chemical modifications such as, e.g., DNA methylation and histone modification. In some embodiments, epigenetic modifications can cause a change in chromatin structure, DNA accessibility, and/or transcription factor binding. In some embodiments, epigenetic modifications can be detected or quantified directly (e.g., by using an agent that binds an epigenetic modification (e.g., an antibody that binds H3K4me3 or H3K27ac)). In some embodiments, epigenetic modifications can be measured indirectly, e.g., by measuring or detecting one or more attributes, changes in which are indicative of changes in epigenetic modifications. For example, in some embodiments, chromatin accessibility and/or transcription factor binding can be used as a measure of epigenetic modifications at a given locus. As used herein, the term “epigenetic marker” refers to an indicator of epigenetic state, and includes, e.g., histone modification, DNA methylation, transcription factor binding, and chromatin accessibility states. As used herein, the term “epigenetic biomarker” refers to an epigenetic marker that can be used in the detection of a disease or condition. [0377] Expression level, amount, or level: As used herein, the terms “expression level,” “amount,” or “level,” or used herein interchangeably, of a biomarker is a detectable level in a biological sample. “Expression” generally refers to the process by which information (e.g., gene-encoded and/or epigenetic) is converted into the structures present and operating in the cell. Therefore, as used herein, “expression” may refer to transcription into a polynucleotide, Attorney Docket No: 2014191-0041 translation into a polypeptide, or even polynucleotide and/or polypeptide modifications (e.g., posttranslational modification of a polypeptide). Fragments of the transcribed polynucleotide, the translated polypeptide, or polynucleotide and/or polypeptide modifications (e.g., posttranslational modification of a polypeptide) shall also be regarded as expressed whether they originate from a transcript generated by alternative splicing or a degraded transcript, or from a post-translational processing of the polypeptide, e.g., by proteolysis. “Expressed genes” include those that are transcribed into a polynucleotide as mRNA and then translated into a polypeptide, and also those that are transcribed into RNA but not translated into a polypeptide (for example, transfer and ribosomal RNAs). Expression levels can be measured by methods known to one skilled in the art and also disclosed herein. The expression level or amount of a biomarker can be used to identify/characterize a subject having a breast cancer (e.g., an HR+ breast cancer (e.g., an ER+ breast cancer (e.g., luminal A breast cancer or luminal B breast cancer)), DCIS, and/or a metastatic or a locally advanced breast cancer) who may be likely to respond to, or benefit from, a particular therapy (e.g., a therapy comprising an endocrine therapy, e.g., a SERM (e.g., a SERD), a GnRH agonist, and/or an AI). The expression level or amount of a biomarker provided herein in a subject having a breast cancer described herein can also be used to determine and/or track the benefit of an administered endocrine therapy over time. [0378] ER Pathway Activity: As used herein, the terms “ER pathway activity” or “ER activity” refer to the degree of activation of the Estrogen Receptor (ER) signaling pathway (e.g., in a cancer sample, a tissue sample, or a cell). While ER pathway activity is associated with ER expression, the two are not always directly correlated (e.g., as discussed elsewhere in the present disclosure (e.g., in some embodiments). In some embodiments, methods provided herein can provide a more accurate measure of ER pathway activity than a measurement of ER expression. In some embodiments, methods provided herein can provide a more accurate measure of ER dependence than a measurement of ER expression. In some embodiments, ER activity refers to signaling activity that is induced by ER activation. In some embodiments, ER pathway activity refers to estrogen-induced activation of ER signaling (i.e., ER activity that results from estrogen activation). In some embodiments, estrogen-induced activation is a measure of a cancer’s dependence on ER activity for continued growth, and therefore susceptibility to ER-targeted therapies. [0379] In some embodiments, ER pathway activity can be determined using a method Attorney Docket No: 2014191-0041 that comprises measuring expression of one or more genes (e.g., one or more genes listed in any one of Tables 1-8) whose expression is promoted or repressed by activation of ER (e.g., wherein expression is measured by measuring protein expression, transcription (e.g., using an RNA-seq method), and/or epigenetic modifications (e.g., promoter signal and/or enhancer signal)). In some embodiments, ER pathway activity can be measured using a method provided herein. In some embodiments, ER pathway activity in a cancer in a subject can be determined by obtaining a biological sample from the subject (e.g., a sample comprising cfDNA, a blood sample, and/or a serum sample). [0380] ER Activity Score: As used herein, the terms “ER activity score” and “ER pathway activity score” refer to a numerical value that reflects the sum of (i) the ratio of promoter signal at promoter regions of genes induced by activation of the ER signaling pathway to promoter signal at promoter regions of genes repressed by activation of the ER signaling pathway, and (ii) the ratio of enhancer signal at enhancer regions of genes induced by activation of the ER signaling pathway to enhancer signal at enhancer regions of genes repressed by activation of the ER signaling pathway. In some embodiments, ratios (i) and (ii) are scaled prior to summing. In some embodiments, scaling entails adjusting scores such that the maximum and minimum enhancer signal scores have the same value as the maximum and minimum promoter scores (e.g., 0 and 1). ER pathway activity scores can be used, e.g., as a predictive, prognostic, and/or pharmacodynamic biomarker (e.g., to identify an individual having cancer (e.g., breast cancer), an individual who is likely to benefit from a therapy comprising an ER-targeting agent, or to monitor responsiveness of an individual having a cancer (e.g., breast cancer) to a treatment comprising administering an ER-targeted agent). [0381] The terms “reference ER pathway activity score” and “reference ER activity score” refer to an ER pathway activity score against which another ER pathway activity score is compared, e.g., to make a predictive, prognostic, and/or therapeutic determination. For example, the reference ER pathway activity score may be an ER pathway activity score determined for a reference sample, an ER pathway activity score determined for a reference population (e.g., a population of patients (i) with ER+ breast cancer (e.g., as determined by IHC), (ii) with ER- negative cancer (e.g., as determined by IHC), (iii) with mESR1 breast cancer, (iv) who are healthy subjects and/or who have been determined to be cancer free, (iv) who have previously been found to respond to treatment with a given ER-targeting agent, or (v) who have previously Attorney Docket No: 2014191-0041 found to not respond to treatment with a given ER-targeting agent). In some embodiments, the reference ER pathway activity score is an ER pathway activity score measured from a sample obtained from the same subject and obtained at an earlier point in time. In some embodiments, the reference ER pathway activity score is a pre-determined value. [0382] In some instances, the reference ER pathway activity score is a cut-off value that significantly separates individuals having a cancer (e.g., breast cancer) with ER pathway activity from individuals having a cancer (e.g., breast cancer) with low or no ER pathway activity (e.g., a reference ER pathway activity score that is at or above 0.25 (e.g., 0.25 to about 2.00, about 0.30 to about 2.00, about 0.35 to about 2.00, about 0.40 to about 2.00, about 0.45 to about 2.00, about 0.50 to about 2.00, about 0.55 to about 2.00, or about 0.60 to about 2.00). In some instances, the reference ER pathway activity score is a cut-off value that significantly separates individuals having a cancer (e.g., breast cancer) that are likely to respond to a therapy including an ER- targeting agent (e.g., as described herein) from those who are not likely to respond to a therapy including an ER-targeting agent. It will be appreciated by one skilled in the art that the numerical value for the reference ER pathway activity score may vary depending on the type of cancer (e.g., an HR+ breast cancer (e.g., an ER+ breast cancer (e.g., luminal A breast cancer or luminal B breast cancer)), DCIS, and/or a metastatic or a locally advanced breast cancer), the methodology used to measure an ER pathway activity score, the specific gene signatures examined (e.g., the combination of genes set forth in one or more of Table 1-8), and/or the statistical methods used to generate an ER pathway activity score. For example, the activity score described herein can be calculated by calculating a z-score for a reference population and using the formula provided in the paragraph that immediately follows to re-scale the expression of each gene across the samples to a mean of 0 and a standard deviation of 1. The expression data for a given patient can then be overlayed onto the z-scored reference space as described herein. [0383] In some embodiments, a z score may be described by the formula: z = (x - m) / s, where z is the rescaled score, x is, e.g., a measure of regulatory signal (e.g., promoter or enhancer signal), m is the mean regulatory signal calculated from a reference population; and s is the standard deviation for the regulatory signal calculated from a reference population. [0384] In some embodiments, ER activity score is corrected for ctDNA%. A person of skill in the art would understand approaches that could be used for correction. An exemplary Attorney Docket No: 2014191-0041 method for correcting for ctDNA% is provided in Example 1 of the present application. [0385] Identity: As used herein, the term “identity” refers to the overall relatedness between polymeric molecules, e.g., between nucleic acid molecules (e.g., DNA molecules) and/or between polypeptide molecules. Methods for the calculation of a percent identity as between two provided sequences are known in the art. The term “% sequence identity” refers to a relationship between two or more sequences, as determined by comparing the sequences. In the art, “identity” also means the degree of sequence relatedness between protein and nucleic acid sequences as determined by the match between strings of such sequences. “Identity” (often referred to as “similarity”) can be readily calculated by known methods, including those described in: Computational Molecular Biology (Lesk, A. M. ed.) Oxford University Press, NY (1988); Biocomputing: Informatics and Genome Projects (Smith, D. W. ed.) Academic Press, NY (1994); Computer Analysis of Sequence Data, Part I (Griffin, A. M. and Griffin, H. G. eds.) Humana Press, NJ (1994); Sequence Analysis in Molecular Biology (Von Heijne, G. ed.) Academic Press (1987); and Sequence Analysis Primer (Gribskov, M. and Devereux, J. eds.) Oxford University Press, NY (1992), each of which are separately incorporated by reference in their entirety. Preferred methods to determine identity are designed to give the best match between the sequences tested. Methods to determine identity and similarity are codified in publicly available computer programs. For example, calculation of the percent identity of two nucleic acid or polypeptide sequences can be performed by aligning the two sequences (or the complement of one or both sequences) for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second sequences for optimal alignment and non- identical sequences can be disregarded for comparison purposes). The nucleotides or amino acids at corresponding positions are then compared. When a position in the first sequence is occupied by the same residue (e.g., nucleotide or amino acid) as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, optionally accounting for the number of gaps, and the length of each gap, which may need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a computational algorithm, such as BLAST (basic local alignment search tool). Sequence alignments and percent identity calculations may be performed using the Megalign program of Attorney Docket No: 2014191-0041 the LASERGENE bioinformatics computing suite (DNASTAR, Inc., Madison, Wisconsin). Multiple alignment of the sequences can also be performed using the Clustal method of alignment (Higgins and Sharp, Comp Appl Biosci (1989) 5(2):151-153), incorporated by reference herein in its entirety, with default parameters (GAP PENALTY=10, GAP LENGTH PENALTY=10). Relevant programs also include the GCG suite of programs (Wisconsin Package Version 9.0, Genetics Computer Group (GCG), Madison, Wisconsin); BLASTP, BLASTN, BLASTX (Altschul et al., J Mol Biol (1990) 215:403-410); DNASTAR (DNASTAR, Inc., Madison, Wisconsin); and the FASTA program incorporating the Smith- Waterman algorithm (Pearson, Comput Methods Genome Res [Proc Int Symp] (1994), Meeting Date 1992, 111-120. Eds. Suhai, Sandor. Plenum, New York, NY (the contents of each of which is separately incorporated herein by reference in its entirety). Within the context of this disclosure, it will be understood that where sequence analysis software is used for analysis, the results of the analysis are based on the “default values” of the program referenced. “Default values” will mean any set of values or parameters, which originally load with the software when first initialized. [0386] “Improve,” “increase,” “inhibit,” or “reduce”: As used herein, the terms “improve”, “increase”, “inhibit”, and “reduce”, and grammatical equivalents thereof, indicate qualitative or quantitative difference from a reference. [0387] Methylation Status: As used herein, “methylation status” of a genomic locus refers to the frequency with which DNA sequences corresponding to the genomic locus are identified in an assay for detection of DNA methylated sequences and/or the density (e.g., the measured density) of DNA methylation corresponding to the genomic locus. Methylation status can be determined by various assays known in the art, including without limitation Bisulfite sequencing (BS-Seq), Whole Genome Bisulfite Sequencing (WGBS), Methylated DNA ImmunoPrecipitation sequencing (MeDIP-seq), or Methyl-CpG-Binding Domain sequencing (MBD-seq). Where two samples are separately analyzed by the same assay or comparable assays for detection of DNA methylated sequences, differences in methylation status of genomic loci can be detected. Methylation status can be compared to a standard or reference. A sample that has a methylation status that differs from a standard or reference can be referred to as differentially modified. [0388] “Modification Status” or “Histone Modification Status”: As used herein, Attorney Docket No: 2014191-0041 “modification status” or “histone modification status” of a genomic locus refers to the frequency with which DNA sequences corresponding to the genomic locus are identified in an assay for detection of DNA sequences associated with histones bearing one or more histone modifications (e.g., one or more particular histone modifications) and/or the density (e.g., the measured density) of histone modifications (e.g., one or more particular histone modifications) corresponding to the genomic locus. Modification status can be determined by various assays known in the art, including without limitation ChIP-seq as one example. Other well-known assays include CUT&RUN (Cleavage Under Targets and Release Using Nuclease) sequencing and CUT&Tag (Cleavage Under Targets and Tagmentation). Where two samples are separately analyzed by the same assay or comparable assays for detection of DNA sequences associated with histones bearing one or more histone modifications (e.g., one or more particular histone modifications), differences in modification status of genomic loci can be detected. Modification status can be compared to a standard or reference. A sample that has a modification status that differs in modification status or histone modification status from a standard or reference can be referred to as differentially modified. [0389] Promoter signal: As used herein, the term “promoter signal” refers to an epigenetic modification in a promoter region that is associated with increased expression of a gene regulated by the promoter region. Examples of such promoter signals are known in the art, and include, e.g., histone methylation (e.g., H3K4 methylation (e.g., H3K4me3)). In some embodiments, promoter signal can be measured by quantifying histone methylation (e.g., H3K4me3), chromatin accessibility, and/or transcription factor binding. [0390] Regulatory sequence: As used herein in the context of expression of a nucleic acid coding sequence, a regulatory sequence is a nucleic acid sequence that controls expression of a coding sequence, e.g., a promoter sequence or an enhancer sequence. In some embodiments, a regulatory sequence can control or impact one or more aspects of gene expression (e.g., cell-type-specific expression, inducible expression, etc.). [0391] Subject: As used herein, the term “subject” refers to an organism, typically a mammal (e.g., a human). In some embodiments, a subject is suffering from a disease, disorder or condition (e.g., ER-positive cancer, e.g., ER-positive breast cancer, etc.). In some embodiments, a subject is susceptible to a disease, disorder, or condition. In some embodiments, a subject displays one or more symptoms or characteristics of a disease, disorder or condition. In Attorney Docket No: 2014191-0041 some embodiments, a subject is not suffering from a disease, disorder or condition. In some embodiments, a subject does not display any symptom or characteristic of a disease, disorder, or condition. In some embodiments, a subject has one or more features characteristic of susceptibility to or risk of a disease, disorder, or condition. In some embodiments, a subject is a subject that has been tested for a disease, disorder, or condition, and/or to whom therapy has been administered. In some instances, a human subject can be interchangeably referred to as a “patient” or “individual”. [0392] Therapeutic agent: As used herein, the term “therapeutic agent” refers to any agent that elicits a desired pharmacological effect when administered to a subject. In some embodiments, an agent is considered to be a therapeutic agent if it demonstrates a statistically significant effect across an appropriate population. In some embodiments, the appropriate population can be a population of model organisms or a human population. In some embodiments, an appropriate population can be defined by various criteria, such as a certain age group, gender, genetic background, preexisting clinical conditions, etc. In some embodiments, a therapeutic agent is a substance that can be used for treatment of a disease, disorder, or condition (e.g., ER-positive cancer, e.g., ER-positive breast cancer, etc.). In some embodiments, a therapeutic agent is an agent that has been or is required to be approved by a government agency before it can be marketed for administration to humans. In some embodiments, a therapeutic agent is an agent for which a medical prescription is required for administration to humans. [0393] Therapeutically effective amount: As used herein, “therapeutically effective amount” refers to an amount that produces the desired effect for which it is administered. In some embodiments, the term refers to an amount that is sufficient, when administered to a population suffering from or susceptible to a disease, disorder, and/or condition (e.g., ER- positive cancer, e.g., ER-positive breast cancer, etc.) in accordance with a therapeutic dosing regimen, to treat the disease, disorder, and/or condition. In some embodiments, a therapeutically effective amount is one that reduces the incidence and/or severity of, and/or delays onset of, one or more symptoms of the disease, disorder, and/or condition. Those of ordinary skill in the art will appreciate that the term “therapeutically effective amount” does not in fact require successful treatment be achieved in a particular individual. Rather, a therapeutically effective amount may be that amount that provides a particular desired pharmacological response in a significant number of subjects when administered to patients in need of such treatment. In some Attorney Docket No: 2014191-0041 embodiments, reference to a therapeutically effective amount may be a reference to an amount as measured in one or more specific tissues (e.g., a tissue affected by the disease, disorder or condition) or fluids (e.g., blood, saliva, serum, sweat, tears, urine, etc.). Those of ordinary skill in the art will appreciate that, in some embodiments, a therapeutically effective amount of a particular agent or therapy may be formulated and/or administered in a single dose. In some embodiments, a therapeutically effective amount of a particular agent or therapy may be formulated and/or administered in a plurality of doses, for example, as part of a dosing regimen. [0394] Treatment: As used herein, the term “treatment” (also “treat” or “treating”) refers to administration of a therapy that partially or completely alleviates, ameliorates, relieves, inhibits, delays onset of, reduces severity of, and/or reduces incidence of one or more symptoms, features, and/or causes of a particular disease, disorder, or condition, or is administered for the purpose of achieving any such result. In some embodiments, such treatment can be of a subject who does not exhibit signs of the relevant disease, disorder, or condition and/or of a subject who exhibits only early signs of the disease, disorder, or condition (e.g., cancer having high ER activity, e.g., breast cancer having a high ER activity, etc.). Alternatively, or additionally, such treatment can be of a subject who exhibits one or more established signs of the relevant disease, disorder and/or condition. In some embodiments, treatment can be of a subject who has been diagnosed as suffering from the relevant disease, disorder, and/or condition. In some embodiments, treatment can be of a subject known to have one or more susceptibility factors that are statistically correlated with increased risk of development of the relevant disease, disorder, or condition. A “prophylactic treatment” includes a treatment administered to a subject who does not display signs or symptoms of a condition to be treated or displays only early signs or symptoms of the condition to be treated such that treatment is administered for the purpose of diminishing, preventing, or decreasing the risk of developing the condition. Thus, a prophylactic treatment functions as a preventative treatment against a condition. A “therapeutic treatment” includes a treatment administered to a subject who displays symptoms or signs of a condition and is administered to the subject for the purpose of reducing the severity or progression of the condition. EXAMPLES [0395] The present Examples demonstrate the identification and use of differentially Attorney Docket No: 2014191-0041 modified and/or differentially accessible genomic loci in cell lines with different ER activities and/or from cfDNA in plasma samples obtained from subjects having breast cancer with different ER activities. The present Examples show that differentially modified and/or differentially accessible genomic loci of the present disclosure can be used to determine ER activity from cfDNA in plasma samples obtained from subjects with ER-positive and ER- negative cancers. Example 1: Materials and Methods [0396] This Example describes the materials and methods that were used to generate sequencing data that was then used in Example 2 to determine ER activity scores. Materials [0397] Plasma samples: Samples were obtained from 44 patients previously determined to have metastatic breast cancer. Blood samples were collected within 6 weeks of tumor biopsy, with ER expression status determined using immunohistochemistry (IHC). [0398] Plasma samples were prepared from whole blood collected in EDTA blood collection tubes or Streck cell-free DNA BCT with 4-6 hours of collection and plasma was _{stored at - Whole blood was obtained from breast cancer patients under a protocol} approved by an IRB. Breast cancer patients had previously been determined to be ER-positive or ER-negative. Informed content was obtained in each case and samples were de-identified. Methods Chromatin immunoprecipitation (ChIP) [0399] An exemplary protocol for performing chromatin immunoprecipitation (ChIP) for histone marks (H3K4me3 and H3K27ac) in cell lines is provided, e.g., in Schones et al., Cell (2008) 132(5):887-898, which is incorporated by reference herein in its entirety. Briefly, cells are lysed and chromatin is MNase digested to generate approximately 80% mononucleosomes. Nucleosomes are then incubated with antibodies that bind H3K4me3 modifications or H3K27ac modifications that were previously conjugated to magnetic epoxy beads (Invitrogen) with constant mild shaking overnight. The beads are then washed and rinsed. Sequencing libraries Attorney Docket No: 2014191-0041 are generated from purified immunoprecipitated sample DNA and then sequenced. [0400] Chromatin immunoprecipitation (ChIP) for histone marks (H3K4me3 and H3K27ac) in plasma samples was performed using methods similar to those previously described in Sadeh et al., Nat Biotechnol (2021) 39: 586-598 and Jang et al., Life Sci Alliance (2023) 6(12):e202302003. Briefly, about 1 mL frozen plasma was thawed and then prepared for ChIP. The thawed plasma was incubated with antibodies that bind H3K4me3 modifications or H3K27ac modifications that were previously conjugated to magnetic epoxy beads (Invitrogen) with constant mild shaking overnight. The beads were then washed and rinsed. Sequencing libraries were generated from purified immunoprecipitated sample DNA and then sequenced. ChIP-seq and DNA methylation data analysis [0401] ChIP-sequencing reads were aligned to the human genome build hg19 using the Burrows-Wheeler Aligner (BWA) version 0.7.15. Non-uniquely mapping and redundant reads were discarded. [0402] The ER activity score presented in Example 2 utilized the 21 estrogen-induced and 17 estrogen-repressed genes provided in Supplementary Table 2 of Guan et al., Cell (2019) 178(4):949-963. The promoter of each gene provided in Table 1 was defined as a 2 kb region centered over the gene’s TSS. Enhancers of each gene were determined using the breast epithelium enhancer predictions from the ENCODE consortium (https://www.encodeproject.org/annotations/ENCSR106ORM/, https://www.encodeproject.org/annotations/ENCSR125OUM/, https://www.encodeproject.org/annotations/ENCSR476PNY/, https://www.biorxiv.org/content/10.1101/2023.11.09.563812v1.full), which were downloaded and converted from hg38 to hg19. ‘SelfPromoter’ predictions were then removed and overlapping regions across the 3 prediction sets were merged (regions provided in Table 2). [0403] Counts of H3K4me3 ChIP-seq sequencing fragments (reads) overlapping genome-wide promoters (all promoters genome-wide) were corrected for local ChIP-seq background (to improve signal-to-noise) and quantile normalized (to normalize sample-to- sample variability). If multiple promoters existed for a given gene, the promoter with the largest difference in reads between ER positive and ER negative samples was retained. The promoter and activation signal for each sample was calculated as the ratio of quantile-normalized reads at Attorney Docket No: 2014191-0041 promoters of estrogen-induced genes (21 genes) / estrogen-repressed genes (17 genes). H3K27ac ChIP-seq reads over all enhancer regions genome-wide were similarly normalized. The enhancer activation signal for each sample was calculated as the ratio of quantile-normalized H3K27ac reads at enhancers associated with estrogen-induced genes (21 genes) / enhancers associated with estrogen-repressed genes (17 genes). In order to weight promoters and enhancers equally, the distributions of enhancer and promoter ratios across the population were scaled such that the min/max of both distributions were 0/1. The scaled enhancer/promoter ratios were then summed to generate the ER activation score. To correct the ER activation score for ctDNA%, the ichorCNA estimated values for each sample was determined, and the ER activation score was regressed against the estimated ctDNA% with standard linear regression in only the ER+ sample subset. The predicted activation score due to ctDNA% was then subtracted from the actual ER activation score for the entire cohort to produce the ctDNA-corrected score. [0404] The association between ER activity score and ER status as determined by IHC was assessed using the Wilcoxon rank-sum test. For IHC, ER expression 1% was considered positive. Example 2: Determination of ER Activation Score in Plasma Samples [0405] The present example provides data demonstrating that technologies described in the present application can be used to determine ER activity in cancer using only a small volume of a sample containing cfDNA (e.g., a plasma sample). Methods and materials used in the present application are described in Example 1. [0406] The ER activity score algorithm described in Example 1 was applied to samples with detectable ctDNA (19 of the 44 samples obtained). 3 of the 19 samples (16%) were collected from patients who were ER+ at primary diagnosis and ER- (ER-negative) at a later time point. [0407] Figs.3(A) and 3(B) demonstrate that methods described herein can be used to determine ER activity, with samples obtained from ER+ patients (as determined by IHC) shown to consistently have a higher ER activity score as compared to samples obtained from ER- patients. Fig.3(C) further demonstrates that promoter signal determined using methods provided herein correlates with ER expression status, with samples from subjects with high ER expression consistently shown to have higher promoter signal as compared to samples obtained Attorney Docket No: 2014191-0041 from ER+ patients with lower ER expression. Samples from both groups of ER+ subjects were also shown to have a higher ER activity score as compared to samples from ER- patients. [0408] Fig.4 shows that an association between ER activity score and ER/HER2 status was also observed using methods described herein. In particular, samples obtained from HER2+ subjects were consistently found to have lower ER activity scores as compared to samples obtained from HER2- subjects, for samples obtained from both ER+ and ER- subjects. This observation is consistent with previous observations that there may be “crosstalk” between ER and HER2 pathways. See, e.g., Pegram et al., NPJ Breast Cancer (2023) 9(1):45, the contents of which are incorporated by reference herein in their entirety. The results provided in Fig.4, however, represent the first data showing epigenetic difference depending on ER/HER2 status. Without wishing to be bound by theory, changes in the epigenome could be due to, e.g., reorganization of the ER pathway or lower ER expression. Fig.4(B) shows average Z-scores of Enhancer/Promoter signal in the enhancers and promoters of estrogen induced genes. Enhancer and promoter signal at a group of genes that includes GREB1, ZNF703, and IGFBP4 was found to drive in part the higher activity scores in ER+/HER2- patients. Fig.4(C) shows average Z- scores of Enhancer/Promoter signal in the enhancers and promoters of estrogen repressed genes. Signal at enhancers and promoters at a group of genes that includes TGFB3, CCNG2, and PNPLA7 were found to drive lower activity scores in ER+/HER2+ patients. Thus, the results provided in the present example demonstrate the ability of methods provided herein to provide both useful new insights into biological mechanisms that underlie different cancerous states as well as better inform therapeutic strategies. [0409] Fig.5(A) shows that technologies provided herein are also capable of detecting changes in ER activity over time. In particular, Fig.5(A) shows results from samples obtained at two points in time: upon initial diagnosis and a later point in time, following treatment. Three patients were ER+ upon initial diagnosis, and later became ER-. Methods provided herein were capable of detecting the change in ER activation score for each patient, demonstrating that technologies provided herein can be used to track ER expression status over time, which can be useful, e.g., for changing therapies if a change in ER activity score is detected. Fig.5(B) shows that technologies provided herein detected increased ER activity in samples obtained from patients having an mESR1 mutation (mutant ESR1, corresponding to patients having an activating mutation in the ESR1 gene) as compared to samples obtained from patients in which Attorney Docket No: 2014191-0041 such a mutation had not been detected. Surprisingly, samples from a subpopulation of subjects in which no mutation associated with increased ER activity was detected were found to exhibit high ER activity, and therefore may benefit from treatment with ER-targeted agents (e.g., may benefit from a treatment protocol that is similar to that administered to patients having an mESR1 mutation). These results demonstrate that the methods provided herein can be useful for identifying new patient populations that may benefit from ER targeting agents (e.g., SERDs). In particular, patients who do not have a mutation that is associated with increased ER activity, but which nonetheless have elevated ER activity. [0410] Fig.6. shows that patients who have received more lines of therapeutics (in particular, >4 lines of endocrine therapy) displayed lower ER activity scores as compared to patients who received fewer lines of therapy. This observation is consistent with the understanding in the field and demonstrates that technologies provided herein both (i) reflect biological differences in cancers, and (ii) can be used to inform therapeutic treatments, and lead to improved therapeutic outcomes. Conclusions [0411] The present Example provides data generated using a novel, liquid biopsy-based epigenomic activity score to predict ER signaling activity using a small volume of plasma. The methods provided herein would be useful, e.g., for providing a minimally invasive tool to help guide treatment selection for patients with ER+ breast cancer and predict response to novel ER targeting agents. Example 3: Epigenomic Characterization of ER Transcriptional Activation via Liquid Biopsy. [0412] The present Example describes an experiment in which histone modification levels (H3K27ac and H3K4me3) were used to measure ER activity (including ER dependence) in breast cancer cell lines that had been incubated with or deprived of estrogen. Changes in promoter and enhancer signal were detected for genes known to be associated with ER activity, demonstrating that methods described herein accurately reflect intracellular pathway activity. [0413] Comparing differentially modified loci, a “core” set of loci that were differentially modified in the presence of estrogen as compared to its absence were also identified in multiple cell lines. Without wishing to be bound by theory, the core set of loci is thought to be more Attorney Docket No: 2014191-0041 broadly applicable to breast cancer patients as compared to differentially modified loci identified in a single cell line, given (as demonstrated by data provided in the present Example) the significant variation in signal observed between difference breast cancer cell lines. Genomic loci identified in the cell line experiment was used to assess ER activity (including ER dependence) in plasma samples from breast cancer patients. Materials [0414] Plasma samples: Samples were obtained from 54 patients previously determined to have metastatic breast cancer (summarized in the table provided in Fig.7). Samples were collected at Knight Cancer Institute, Oregon Health Sciences University (OHSU). Blood samples were collected within 1 week of tumor biopsy, with ER status determined using immunohistochemistry (IHC). [0415] Plasma samples were prepared from whole blood collected in EDTA blood collection tubes or Streck cell-free DNA BCT with 4-6 hours of collection and plasma was _{stored at - breast cancer patients under a protocol} approved by an IRB. Breast cancer patients had previously been determined to be ER-positive or ER-negative. Informed content was obtained in each case and samples were de-identified. [0416] Cell lines: A panel of 8 ER+ breast cancer cells lines (MCF7, T47D, BT483, CAMA1, HCC1428, ZR-75-1, BT474, MDA-MB-361) with diversity of breast cancer classification markers progesterone receptor (PGR) and HER2 (see chart in Fig.8) were cultured in normal serum (which contains estrogen) and then plated in media supplemented with charcoal stripped serum for 24 hours prior to the addition of either 0.1 nM estradiol (E2) or vehicle. Cells were then harvested between 40-48 hours after E2 treatment and aliquoted into 5M cells/vial. Methods Chromatin immunoprecipitation (ChIP) [0417] Fragmented cell-line ChIP-seq: Cells stored at -80^o C were thawed and counted using a Countess 3 cell counter (ThermoFisher Scientific). Enzymatically fragmented chromatin was prepared from 1 x 10^6 cells using reagents from the Nucleosome Preparation Kit (Active Motif, 53504) with the following protocol modifications used to optimize fragmentation. Cells were washed 3X with PBS, lysed using 500 uL lysis buffer supplemented with 2.5 uL protease inhibitor cocktail and 2.5 uL 100 mM PMSF for 30 minutes on ice, nuclei pelleted by centrifugation at 2500 g x 10 min at 4C. Enzymatic fragmentation used 2 uL of 200 U/mL Attorney Docket No: 2014191-0041 enzymatic shearing cocktail with digestion at 37^oC for 30 minutes. The enzymatic reaction was stopped with 3.5 uL of 0.5M EDTA. The digested chromatin was cleared by centrifugation at 18,000 x g for 5 minutes at 4^oC. To assess efficiency of digestion, 50 uL of the reaction underwent DNA extraction and QC for size and concentration using the cell-free DNA ScreenTape assay on the Agilent 4200 TapeStation system. The average fragment size of the digestion was 187 bp (23% CV) with >95% region in the mono- and di-nucleosome profile and majority in the target mononucleosomal size bin.100 ng of the digested chromatin was suspended in 1 mL of 1X ChIP buffer (Cell Signaling Technologies, 7008) supplemented with 1X cOmplete EDTA-free protease inhibitor cocktail (Roche, 11873580001) and processed through epigenomics assays. Nucleosomes are then incubated with antibodies that bind H3K4me3 modifications or H3K27ac modifications that were previously conjugated to magnetic epoxy beads (Invitrogen) with constant mild shaking overnight. The beads are then washed and rinsed. Sequencing libraries are generated from purified immunoprecipitated sample DNA and then sequenced. [0418] Plasma ChIP-seq: Chromatin immunoprecipitation (ChIP) for histone marks (H3K4me3 and H3K27ac) in plasma samples was performed using methods similar to those previously described in Sadeh et al., Nat Biotechnol (2021) 39: 586-598 and Jang et al., Life Sci Alliance (2023) 6(12):e202302003. Briefly, about 1 mL frozen plasma was thawed and then prepared for ChIP. The thawed plasma was incubated with antibodies that bind H3K4me3 modifications or H3K27ac modifications that were previously conjugated to magnetic epoxy beads (Invitrogen) with constant mild shaking overnight. The beads were then washed and rinsed. Sequencing libraries were generated from purified immunoprecipitated sample DNA and then sequenced. Methylated DNA enrichment [0419] Enrichment of DNA methylation was performed on DNA extracted from cell lines and human plasma samples using the EpiMark® Methylated DNA Enrichment Kit (E2600S, available from New England Biolabs) following the manufacturer’s protocol. Briefly, cfDNA libraries were prepared and adaptors ligated. Then, the EpiMark® capture reagent was applied to each library sample following the manufacturer’s protocol. Enriched DNA libraries Attorney Docket No: 2014191-0041 were amplified and sequenced. ChIP-seq and DNA methylation data analysis [0420] ChIP-sequencing reads and MBD-sequencing reads were aligned to the human genome build hg19 using the Burrows-Wheeler Aligner (BWA) version 0.7.15. Non-uniquely mapping and redundant reads were discarded. [0421] Cell Line Analysis: ChIP/MBD peaks (local enrichments) were called using the MACS2 package, and fragments (reads) overlapping peaks were corrected for local ChIP-seq background (to improve signal-to-noise) and quantile normalized (to normalize sample-to- sample variability). Peaks with differential signal across E2/veh conditions were identified using DEseq2. [0422] ER Dependence Index Score: A diagram summarizing an exemplary method for determining an ER dependence index score on the basis of epigenetic modifications is provided in Fig.11. Peaks were called on H3K27ac ChIP-seq performed on plasma from ER+ mBC patients using MACS2. Fragments overlapping these regions were corrected for local ChIP-seq background (to improve signal-to-noise) and quantile normalized (to normalize sample-to- sample variability). These regions were then tested for significantly differential signal in the E2 vs vehicle (veh) conditions of the cell line experiments described above. The index score was calculated by taking the difference of two terms: a minuend and subtrahend. The minuend was composed of genomic regions which: (1) have increased signal in E2 treated cells as compared to veh cells, (2) are within 2 kb of ER binding sites (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM2305313), (3) are within 200 kb of ET resistance downregulated genes (https://www.gsea- msigdb.org/gsea/msigdb/human/geneset/MASSARWEH_TAMOXIFEN_RESISTANCE_DN.ht ml?ex=1, https://www.gsea- msigdb.org/gsea/msigdb/human/geneset/CREIGHTON_ENDOCRINE_THERAPY_RESISTAN CE_1.html, https://www.gsea- msigdb.org/gsea/msigdb/human/geneset/CREIGHTON_ENDOCRINE_THERAPY_RESISTAN CE_4.html?ex=1), and (4) not within 2 kb of FOXA1 binding in tamoxifen resistant model (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1945031). The subtrahend is composed of genomic regions which (1) have increased signal in veh treated cells as compared to E2 treated cells and (2) are within 2 kb of a FOXA1 binding site Attorney Docket No: 2014191-0041 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1945030). The minuend and subtrahend are calculated by taking the geometric mean of the background corrected, quantile normalized counts of fragments overlapping each set of regions. The ER dependence index score is calculated as the minuend minus the subtrahend. Results [0423] RNA-seq data was collected for each of the ER+ and ER- cell lines listed in Fig. 8. Results are shown in Figs.9(A)-(C). Fig.9(A) provides a principal component analysis of the collected RNA-Seq data, and shows a clustering of each of the cell lines and a stratification of samples by HER2 status (see PC1 axis). Fig.9(B) provides a differential expression analysis, and reveals that 799 genes were upregulated in estrogen treated cells and 592 genes were upregulated in estrogen deprived cells. Upregulated genes included known ER response genes, such as GREB1, ZNF703, and RERG. Fig.9(C) provides a gene set enrichment analysis of RNA-seq data. As shown, an expected enrichment of estrogen response gene in cell lines treated with exogenous estrogen was observed. Collectively, the RNA-seq analysis of the cell lines establish that an ER-response was being induced in the cell lines. [0424] Figs.10(A)-(G) provide ChIP-seq data from estrogen treated and estrogen deprived cell lines. Widespread enhancer rearrangement was observed upon estrogen exposure. Fig 10(A) provides MBD-seq results. Surprisingly, a differential DNA methylation analysis across estrogen exposed and deprived states revealed no significantly differential DNA methylation sites. Fig.10(B) provides a differential analysis of promoter signal (H3K4me3) across estrogen exposure states. Several hundred differentially modulated promoter regions were identified, including known ER response genes such as GREB1. [0425] Fig.10(C) provides a gene set enrichment analysis of promoters with differential activity across estrogen exposure states. The analysis revealed an expected enrichment of estrogen response terms in enriched in estrogen exposed cells, in addition to upregulation of EMT pathway genes and downregulation of MYC target genes. Fig.10(D) provides a differential analysis of enhancer signal (H3K27ac) across estrogen exposure states. Thousands of genome-wide enhancers were found to be rearranged in response to exogenous estrogen exposure, including enhancers near known ER response genes like GREB1. [0426] Next, significantly differentially modified enhancers (E2 vs vehicle) were identified in (1) separate models for each individual cell line, and (2) all cell lines in one Attorney Docket No: 2014191-0041 ‘ensemble’ model to identify “core” ER responsive epigenomic loci. Intersection sizes (corresponding to the number of enhancers that appear in each combination of models (e.g., 2243 enhancers appeared in the model built only on the T47D cell line data and no other model, while 410 enhancers appear in both the T47D and ensemble model but no other model) were then determined. Results are provided in Fig.10(E). As shown, enhancer landscape rearrangement in response to estrogen exposure was found to be highly cell type specific. Thus, in some embodiments, analyzing multiple cell lines to identify differentially modified loci can lead to identification of loci that are more likely to reflect estrogen signaling in patient samples as compared to genomic loci identified in a single cell line. [0427] Fig.10(F) provides a visualization of enhancer signal in IGV for enhancers near known response genes, known breast cancer subtype marker genes, and housekeeping genes. Fig.10(G) shows H3K27ac signal measured at enhancer loci associated with GREB1 and FOXA1 for each of the cell lines characterized. [0428] To estimate the limit of quantification associated with methods described herein, 78 patient plasma samples (from subjects with ER+ breast cancer, as determined by IHC, and having >10% ctDNA) were each diluted in silico with sequence reads from 10 healthy patient plasma samples (generating 780 total simulated samples at each simulated ctDNA level). For each original breast cancer sample, an ER dependence score was calculated for each of its 10 dilutions at (simulated) 10% ctDNA. Then, at each ctDNA slice, estrogen dependence scores of the 780 simulated samples were corelated back to the mean estrogen dependence scores at 10% ctDNA (note each set of 10 simulated sample originating from the same real samples will have the same mean value that was correlated back to). Fig.12 provides measures of the correlation between the ER dependence score of the simulated samples and the mean ER Dependence Score per original sample at 10% ctDNA. As shown, an LOQ of 2.15% ctDNA was determined using this estimation method. [0429] ER dependence was measured for each cell line in E2 supplemented and E2 stripped media on the basis of H3K27ac modifications. ER activity was also measured using RNA-seq data, using protocols described in Guan et al., which has previously been shown to be predictive of progression free survival (PFS) response to Giredestrant. As shown in Fig.13, the two measures were found to correlate well, demonstrating that methods described herein that utilize histone modifications to measure ER activity can provide accurate insights into Attorney Docket No: 2014191-0041 intracellular dynamics and can also be used to predict responses to treatment and inform therapy selection. [0430] ER dependence in patient plasma samples having >1.5% ctDNA was then measured. Minuend, subtrahend, and ER dependence index measurements are shown in Fig.14. As shown, plasma samples from mESR1 patients consistently displayed higher ER activity and ERDI scores and lower FOXA1 scores as compared to wtESR1 subjects. [0431] Correlation between RNA-seq score, determined using method that had previously been shown to be predictive of clinical outcomes, was also compared to ER dependence as determined using histone modifications. Results are provided in Fig.15. As shown, the two measures were found to correlate well with one another, demonstrating that methods provided herein can accurately determine ER activity or dependence using cfDNA samples, and are therefore useful, e.g., for predicting patient responses to therapies that target the ER activity pathway, and characterizing intratumorally activity. TABLES [0432] Table 1 provides exemplary genomic loci associated with promoters of the indicated genes that are differentially modified (e.g., comprise increased or decreased H3K4me3 modification) and/or differentially accessible depending on ER activity. Table 2 provides exemplary genomic loci associated with enhancers of the indicated genes that are differentially modified (e.g., comprise increased or decreased H3K27ac modification) and/or differentially accessible depending on ER activity. In each of Tables 1 and 2, “induced” genes refer to genes whose expression is increased by activation of the ER signaling pathway, and “repressed” refers to genes whose expression is repressed by activation of the ER signaling pathway. Table 3 provides exemplary genomic loci that exhibit increased H3K4me3 modifications in breast cancer cell lines incubated with media comprising exogenous estrogen as compared to the same cell lines deprived of estrogen. Table 4 provides exemplary genomic loci that exhibit increased H3K4me3 modifications in estrogen deprived breast cancer cell lines as compared to the same cell lines cultured in the presence of exogenous estrogen. Table 5 provides exemplary genomic loci that exhibit increased H3K27ac modifications in breast cancer cell lines incubated with media comprising exogenous estrogen as compared to the same cell lines deprived of estrogen. Table 6 provides exemplary genomic loci that exhibit increased H3K27ac modifications in Attorney Docket No: 2014191-0041 estrogen deprived breast cancer cell lines as compared to the same cell lines cultured in the presence of exogenous estrogen. Table 7 provides a list of exemplary genes associated with enhancer loci that (i) exhibit increased levels of H3K27ac modifications in cell lines cultured with exogenous estrogen as compared to cell lines deprived of estrogen, (ii) are in close proximity (within 2,000 bp) of a ER-binding site, (iii) are in proximity to a gene that has previously been shown to be repressed in tamoxifen resistant cancers, and (iv) are not in close proximity (not within 2,000 bp) of a FOXA1 binding site previously shown to be associated with tamoxifen resistance. Table 8 lists exemplary genes associated with enhancer loci that (i) exhibit increased levels of H3K27ac modifications in cell lines deprived of exogenous estrogen as compared to cell lines cultured with exogenous estrogen, and (ii) are in close proximity (within 2,000 bp) of a FOXA1 binding site previously shown to be associated with tamoxifen resistance. Table 9 lists exemplary genomic loci that (i) exhibit increased levels of H3K27ac modifications in cell lines cultured with exogenous estrogen as compared to cell lines deprived of exogenous estrogen, (ii) are in close proximity (within 2,000 bp) of a ER-binding site, (iii) are in proximity to a gene that has previously been shown to be repressed in tamoxifen resistant cancers, and (iv) are not in close proximity (not within 2,000 bp) of a FOXA1 binding site previously shown to be associated with tamoxifen resistance. Table 10 lists exemplary genomic loci that (i) exhibit increased levels of H3K27ac modifications in cell lines deprived of estrogen as compared to cell lines cultured with exogenous estrogen, and (ii) which are in close proximity (within 2,000 bp) of a FOXA1 binding site previously shown to be associated with tamoxifen resistance.

Attorney Docket No: 2014191-0041 Table 1: Exemplary genomic loci that exhibit differentially promoter signal depending on the extent of activation of the ER signalling pathway G_{enomic Loci Gene Name Feature Direction} _{chr1:109791640-109793641 CELSR2 Promoter Induced} Attorney Docket No: 2014191-0041 Table 2: Exemplary genomic loci that exhibit differentially enhancer signal depending on the extent of activation of the ER signalling pathway _{Genomic Loci Gene Name Feature Direction} _{chr1:109739908-109741384 CELSR2 Enhancer Induced} Attorney Docket No: 2014191-0041 _{chr15:71371613-71372425 CT62 Enhancer Induced} _{chr15:71373044-71373544 CT62 Enhancer Induced} Attorney Docket No: 2014191-0041 _{chr17:38698344-38699654 IGFBP4 Enhancer Induced} _{chr17:38716363-38716954 IGFBP4 Enhancer Induced} Attorney Docket No: 2014191-0041 _{chr7:2729930-2730430 AMZ1 Enhancer Induced} _{chr7:2747704-2748204 AMZ1 Enhancer Induced} Attorney Docket No: 2014191-0041 _{chr10:74056693-74058521 DDIT4 Enhancer Repressed} _{chr10:74074724-74075826 DDIT4 Enhancer Repressed} Attorney Docket No: 2014191-0041 _{chr6:34095694-34096194 GRM4 Enhancer Repressed} _{chr6:34097502-34098002 GRM4 Enhancer Repressed} Attorney Docket No: 2014191-0041 _{chr7:83285213-83285725 SEMA3E Enhancer Repressed} _{chr7:83306345-83307195 SEMA3E Enhancer Repressed}

Attorney Docket No: 2014191-0041 Table 3: Exemplary genomic loci that exhibit increased levels of H3K4me3 modifications in cell lines incubated with exogenous estrogen as compared to cell lines cultured without exogenous estrogen and/or cell lines deprived of estrogen G_{enomic Loci baseMean log2FoldChange lfcSE stat pvalue padj Gene} _{chr2:11679988-11685550 552.572 1.4329 0.1536 9.330 1.060E-20 6.975E-16 GREB1} _{h17 74 7 71 17 11 14 2 7 E1 4 E11} Attorney Docket No: 2014191-0041 c_{hr8:98565762-98566473 5.455 1.2383 0.2849 4.346 1.383E-05 3.700E-03} _{chr6:2846393-2847122 24.021 0.6841 0.1576 4.340 1.424E-05 3.748E-03 SERPINB1} _{chr6:28611164-28611960 10356 22893 05286 4331 1487E-05 3836E-03} Attorney Docket No: 2014191-0041 c_{hr12:69833726-69835757 14.730 0.7976 0.1981 4.027 5.646E-05 8.909E-03 FRS2} _{chr6:28775597-28776514 19.187 1.5177 0.3775 4.020 5.819E-05 9.143E-03} _{chr17:40779353-40780605 5147 12902 03213 4015 5940E-05 9256E-03 RETREG3} Attorney Docket No: 2014191-0041 c_{hr5:56433414-56434321 19.299 0.7244 0.1938 3.737 1.859E-04 1.896E-02 GPBP1} _{chr8:11646719-11648944 26.519 0.6972 0.1872 3.724 1.960E-04 1.965E-02 FDFT1} _{chr21:46771228-46773726 22856 15123 04065 3720 1991E-04 1985E-02} Attorney Docket No: 2014191-0041 c_{hr11:133085197-133086476 12.848 0.9322 0.2625 3.552 3.829E-04 2.940E-02} _{chr14:95427997-95428786 7.323 1.1422 0.3216 3.552 3.829E-04 2.940E-02} _{chr19:47799271-47800612 5739 12588 03547 3549 3871E-04 2957E-02 C5AR1} ₉ Attorney Docket No: 2014191-0041 c_{hr2:107163672-107164045 4.423 1.1833 0.3445 3.435 5.928E-04 3.728E-02} _{chr3:183841859-183842690 37.740 0.6949 0.2025 3.432 5.990E-04 3.755E-02 EIF2B5} _{chrX:23971116-23971871 7282 09915 02889 3432 5982E-04 3755E-02 CXorf58} Attorney Docket No: 2014191-0041 c_{hr3:27574783-27575884 4.667 0.9925 0.2975 3.336 8.504E-04 4.437E-02 SLC4A7} _{chr6:5996178-5998146 81.504 0.6499 0.1948 3.336 8.511E-04 4.437E-02 NRN1} _{chr20:2748292-2750173 71883 06123 01836 3335 8543E-04 4450E-02 CPXM1}

Attorney Docket No: 2014191-0041 Table 4: Exemplary genomic loci that exhibit increased levels of H3K4me3 modifications in cell lines deprived of exogenous estrogen as compared to cell lines cultured with exogenous estrogen. G_{enomic Loci baseMean log2FoldChange lfcSE stat pvalue padj Gene} _{chr9:129829131-129830977 6.962 -2.212 0.557 -3.974 7.058E-05 1.026E-02} _{h1224 72 4 224 74 47 72 2171 422 1 27 1E 7 241 E 4} Attorney Docket No: 2014191-0041 c_{hr8:71182310-71184184 9.718 -1.361 0.271 -5.025 5.035E-07 3.562E-04} _{chr14:93733176-93734485 9.664 -1.357 0.330 -4.107 4.016E-05 7.422E-03 BTBD7} _{chr14:100513598-100513956 4487 -1 332 0364 -3662 2500E-04 2298E-02 EVL} Attorney Docket No: 2014191-0041 c_{hr11:34103876-34104449 4.109 -1.154 0.350 -3.299 9.703E-04 4.771E-02 NAT10} _{chr2:100671977-100673454 9.677 -1.147 0.342 -3.355 7.949E-04 4.287E-02 AFF3} _{chr2:220967984-220968570 4216 -1 146 0292 -3929 8517E-05 1146E-02} Attorney Docket No: 2014191-0041 c_{hr8:40065760-40066506 6.608 -1.062 0.239 -4.446 8.757E-06 2.719E-03} _{chr9:126684648-126686087 11.193 -1.062 0.300 -3.544 3.940E-04 2.987E-02 DENND1A} _{chr7:51318808-51319896 8817 -1 061 0310 -3 420 6253E-04 3806E-02} Attorney Docket No: 2014191-0041 c_{hrX:16489362-16490730 12.323 -1.002 0.214 -4.692 2.705E-06 1.226E-03} _{chr8:95447464-95449777 27.093 -1.001 0.241 -4.159 3.198E-05 6.398E-03 FSBP} _{chr12:67844875-67845374 5242 -0 999 0237 -4 221 2434E-05 5374E-03} Attorney Docket No: 2014191-0041 c_{hr1:74950319-74951486 5.160 -0.912 0.254 -3.586 3.358E-04 2.782E-02} _{chr1:198197756-198199203 17.575 -0.908 0.201 -4.529 5.939E-06 2.067E-03} _{chr3:33111861-33114241 16 665 -0 908 0181 -5 015 5305E-07 3636E-04 GLB1} ₁ Attorney Docket No: 2014191-0041 c_{hr8:135765426-135767176 17.111 -0.844 0.172 -4.917 8.802E-07 5.363E-04 ZFAT} _{chr11:66408770-66409692 35.854 -0.844 0.186 -4.540 5.615E-06 2.005E-03 RBM4} _{chr8:105975758-105977032 44780 -0 843 0254 -3 324 8864E-04 4517E-02} Attorney Docket No: 2014191-0041 c_{hr1:155665060-155665599 13.064 -0.791 0.202 -3.918 8.937E-05 1.169E-02 DAP3} _{chr15:60678970-60679721 9.149 -0.790 0.232 -3.412 6.451E-04 3.873E-02 ANXA2} _{chr9:134619828-134620972 10 629 -0 789 0215 -3 664 2479E-04 2287E-02 RAPGEF1} Attorney Docket No: 2014191-0041 c_{hr9:115899433-115900647 22.048 -0.727 0.152 -4.770 1.839E-06 9.529E-04 SLC31A2} _{chr1:1477792-1480147 20.027 -0.725 0.205 -3.544 3.937E-04 2.987E-02 TMEM240} _{chr12:116394020-116395052 22208 -0 725 0221 -3 277 1049E-03 4937E-02} Attorney Docket No: 2014191-0041 c_{hr6:79889845-79891726 20.709 -0.681 0.187 -3.648 2.647E-04 2.366E-02} _{chr8:126078648-126079574 19.100 -0.679 0.160 -4.248 2.158E-05 4.965E-03 WASHC5} _{chr17:4751396-4753169 16904 -0 675 0195 -3 462 5369E-04 3546E-02 MINK1} Attorney Docket No: 2014191-0041 c_{hr1:113241200-113242293 17.344 -0.611 0.175 -3.494 4.765E-04 3.349E-02 RHOC} _{chr4:17491781-17493126 22.966 -0.611 0.169 -3.624 2.904E-04 2.521E-02 QDPR} _{chr10:28572491-28574148 16363 -0 609 0163 -3 749 1779E-04 1844E-02 MPP7}

Attorney Docket No: 2014191-0041 Table 5: Exemplary genomic loci that exhibit increased levels of H3K27ac modifications in cell lines incubated with exogenous estrogen as compared to cell lines cultured without exogenous estrogen and/or cell lines deprived of estrogen G_{enomic Loci baseMean log2FoldChange lfcSE stat pvalue padj Symbol} _{chr2:11679311-11685538 657.389 1.453 0.112 12.949 2.394E-38 3.903E-33 GREB1} _{h 1 44 41 444 2 427 2 27 1 1 2 1 4E2 E22 HM A1P7} Attorney Docket No: 2014191-0041 c_{hr9:138294633-138296720 79.787 1.658 0.198 8.386 5.044E-17 1.645E-13} _{chr18:49016313-49020170 34.202 2.623 0.314 8.355 6.529E-17 2.087E-13} _{chr2:64500196-64502128 69052 1405 0170 8280 1227E-16 3847E-13} ₁ Attorney Docket No: 2014191-0041 c_{hr5:131712585-131718292 136.491 1.318 0.179 7.370 1.703E-13 2.696E-10 SLC22A5} _{chr12:89857531-89859804 91.346 1.227 0.167 7.338 2.162E-13 3.357E-10 POC1B} _{chr12:116826957-116830829 214255 1218 0166 7339 2144E-13 3357E-10 MIR4472-2} Attorney Docket No: 2014191-0041 c_{hr11:115341583-115343147 15.801 2.289 0.344 6.645 3.033E-11 3.109E-08 CADM1} _{chr19:41367722-41373255 31.741 2.377 0.358 6.637 3.195E-11 3.255E-08 CYP2A6} _{chr17:55966751-55968933 102393 0883 0134 6609 3875E-11 3923E-08 CUEDC1} Attorney Docket No: 2014191-0041 c_{hr6:15220869-15223465 51.760 0.943 0.152 6.189 6.068E-10 4.558E-07 JARID2} _{chr11:70447578-70451509 119.066 1.325 0.214 6.186 6.190E-10 4.629E-07 SHANK2-AS1} _{chr7:140014194-140017628 97490 1100 0178 6178 6502E-10 4818E-07} Attorney Docket No: 2014191-0041 c_{hr5:173906945-173907551 18.050 1.452 0.247 5.878 4.145E-09 2.466E-06} _{chr14:93508682-93513294 105.021 0.894 0.152 5.873 4.270E-09 2.525E-06 ITPK1-AS1} _{chr6:6748476-6751941 152221 0885 0151 5873 4276E-09 2525E-06} Attorney Docket No: 2014191-0041 c_{hr2:65526236-65529602 183.468 0.774 0.136 5.685 1.309E-08 6.457E-06} _{chr1:51787094-51788766 88.992 0.964 0.170 5.678 1.363E-08 6.690E-06 TTC39A} _{chr9:83551972-83554640 5762 3213 0566 5676 1375E-08 6733E-06} Attorney Docket No: 2014191-0041 c_{hr1:109781239-109784920 141.088 0.769 0.141 5.455 4.888E-08 1.992E-05 CELSR2} _{chr9:138144611-138145796 49.929 0.936 0.172 5.454 4.925E-08 2.002E-05} _{chr4:89098808-89100564 91206 0736 0135 5442 5265E-08 2130E-05 ABCG2} ₈ Attorney Docket No: 2014191-0041 c_{hr4:139829717-139831454 49.351 1.450 0.279 5.196 2.042E-07 6.948E-05} _{chr6:6758565-6760253 147.571 0.750 0.145 5.188 2.126E-07 7.191E-05} _{chr9:138256359-138258816 37745 1385 0267 5187 2133E-07 7198E-05 LINC02907} Attorney Docket No: 2014191-0041 c_{hr2:227018208-227020569 37.696 1.863 0.370 5.038 4.695E-07 1.376E-04 LOC646736} _{chr9:132332401-132333945 90.130 0.753 0.150 5.038 4.710E-07 1.379E-04 C9orf50} _{chr22:39865887-39868208 41431 0796 0158 5035 4784E-07 1393E-04 MGAT3} Attorney Docket No: 2014191-0041 c_{hr19:823470-824374 30.724 1.625 0.332 4.901 9.520E-07 2.404E-04 PLPPR3} _{chr5:154425719-154427489 34.736 0.899 0.183 4.902 9.483E-07 2.404E-04 KIF4B} _{chr8:129188302-129190307 112726 0692 0141 4902 9486E-07 2404E-04 MIR1208} Attorney Docket No: 2014191-0041 c_{hr19:58349031-58351441 46.877 1.281 0.267 4.794 1.635E-06 3.671E-04 ZNF587} _{chr7:33955733-33956447 7.909 1.318 0.275 4.789 1.672E-06 3.745E-04 BMPER} _{chr1:35290240-35292479 62601 0788 0165 4785 1708E-06 3814E-04 GJA4} _S1 Attorney Docket No: 2014191-0041 c_{hr10:44776524-44777646 18.945 0.872 0.185 4.701 2.587E-06 5.241E-04 LINC02881} _{chr14:100533421-100535967 29.096 1.221 0.260 4.701 2.592E-06 5.241E-04 EVL} _{chr16:15581926-15584300 18988 1752 0373 4700 2596E-06 5245E-04 BMERB1} Attorney Docket No: 2014191-0041 c_{hr12:91781584-91782932 19.416 0.922 0.201 4.598 4.259E-06 7.697E-04} _{chr1:38187391-38189885 27.725 0.775 0.169 4.596 4.304E-06 7.753E-04 EPHA10} _{chr19:43768297-43771622 122639 0716 0156 4587 4496E-06 8019E-04 PSG9} Attorney Docket No: 2014191-0041 c_{hr1:230972596-230974765 39.191 1.235 0.274 4.506 6.599E-06 1.063E-03 C1orf198} _{chr11:101200442-101200968 11.600 1.112 0.247 4.505 6.644E-06 1.069E-03} _{chr2:217850251-217850902 11571 1325 0294 4503 6687E-06 1074E-03} ₁ Attorney Docket No: 2014191-0041 c_{hr17:64071856-64073313 19.045 0.960 0.217 4.419 9.893E-06 1.443E-03 CEP112} _{chr11:30368068-30368583 3.481 1.993 0.451 4.413 1.017E-05 1.473E-03 ARL14EP} _{chr14:93499002-93502603 204261 0618 0140 4414 1017E-05 1473E-03 ITPK1-AS1} Attorney Docket No: 2014191-0041 c_{hr17:78020074-78021649 10.095 2.157 0.498 4.331 1.482E-05 1.923E-03 CCDC40} _{chr19:18443276-18445479 35.729 1.397 0.323 4.330 1.494E-05 1.932E-03 PGPEP1} _{chr20:60578049-60580878 86464 1225 0283 4329 1501E-05 1937E-03} Attorney Docket No: 2014191-0041 c_{hr3:52478371-52479525 38.360 0.616 0.144 4.268 1.975E-05 2.387E-03 SEMA3G} _{chr5:173918073-173920349 40.793 0.712 0.167 4.267 1.981E-05 2.389E-03} _{chr12:121362639-121364463 63393 0672 0158 4265 2001E-05 2411E-03 SPPL3} Attorney Docket No: 2014191-0041 c_{hr2:131019678-131020524 34.480 1.061 0.253 4.193 2.758E-05 3.086E-03} _{chr15:88062053-88063605 22.080 1.328 0.317 4.191 2.783E-05 3.101E-03} _{chr2:10435238-10436628 16753 0944 0225 4189 2796E-05 3112E-03 HPCAL1} Attorney Docket No: 2014191-0041 c_{hr3:36953390-36955060 16.008 1.145 0.277 4.125 3.705E-05 3.825E-03 TRANK1} _{chr19:56643520-56644751 23.235 0.934 0.226 4.124 3.720E-05 3.838E-03 ZNF444} _{chr11:1753398-1757252 49493 1182 0287 4124 3726E-05 3842E-03 IFITM10} _L Attorney Docket No: 2014191-0041 c_{hr16:87828426-87829719 24.741 0.975 0.239 4.073 4.637E-05 4.441E-03 KLHDC4} _{chr1:44303989-44305986 45.917 0.896 0.220 4.073 4.644E-05 4.442E-03} _{chr10:17485769-17488241 109687 0688 0169 4073 4649E-05 4442E-03 ST8SIA6} Attorney Docket No: 2014191-0041 c_{hr17:74247520-74249692 33.918 1.241 0.308 4.027 5.659E-05 5.091E-03 RNF157} _{chr8:37424194-37425674 116.949 0.669 0.166 4.024 5.711E-05 5.126E-03} _{chr17:38616199-38619640 46093 0882 0219 4024 5732E-05 5140E-03 IGFBP4} Attorney Docket No: 2014191-0041 c_{hr1:26081490-26084538 31.252 0.801 0.202 3.968 7.257E-05 6.045E-03 SELENON} _{chr12:119662486-119664357 6.610 1.636 0.412 3.966 7.323E-05 6.070E-03 HSPB8} _{chr4:7979836-7981151 38928 0826 0208 3965 7336E-05 6070E-03 ABLIM2} Attorney Docket No: 2014191-0041 c_{hr16:75063074-75064217 25.690 0.919 0.235 3.910 9.229E-05 7.083E-03 ZNRF1} _{chr2:220597919-220598872 6.757 1.380 0.353 3.909 9.254E-05 7.089E-03} _{chr15:74001638-74003709 37163 0970 0248 3908 9301E-05 7121E-03 CD276} Attorney Docket No: 2014191-0041 c_{hr3:133253933-133255814 16.324 1.017 0.264 3.849 1.188E-04 8.437E-03 CDV3} _{chr3:188692157-188694829 35.392 1.000 0.260 3.848 1.190E-04 8.445E-03 TPRG1} _{chr6:35738597-35739657 16199 0860 0224 3848 1190E-04 8445E-03 CLPSL2} ₂ _L Attorney Docket No: 2014191-0041 c_{hr5:134380559-134384960 215.325 0.766 0.201 3.802 1.432E-04 9.590E-03 PITX1} _{chr1:7324938-7327024 17.660 1.435 0.378 3.801 1.442E-04 9.636E-03} _{chr8:36932949-36934311 10639 1245 0328 3801 1441E-04 9636E-03} Attorney Docket No: 2014191-0041 c_{hr11:67777456-67778504 151.435 0.668 0.177 3.764 1.673E-04 1.051E-02 ALDH3B1} _{chr9:132459376-132460468 81.309 0.740 0.197 3.763 1.677E-04 1.053E-02 PRRX2} _{chr11:101211610-101213184 31569 1062 0282 3762 1685E-04 1055E-02} ₂₀ Attorney Docket No: 2014191-0041 c_{hr20:55511452-55512401 24.927 0.920 0.248 3.712 2.052E-04 1.202E-02} _{chr8:102532695-102534234 20.235 0.885 0.239 3.712 2.060E-04 1.205E-02 GRHL2} _{chr8:29661424-29662738 17333 0930 0251 3710 2077E-04 1209E-02} ₁ ₁ Attorney Docket No: 2014191-0041 c_{hr21:44489244-44490652 15.529 1.052 0.288 3.657 2.548E-04 1.385E-02 CBS} _{chr1:207028868-207030358 11.046 1.291 0.353 3.657 2.549E-04 1.385E-02 IL20} _{chr13:40139840-40140793 3015 1631 0446 3657 2554E-04 1387E-02 LHFPL6} Attorney Docket No: 2014191-0041 c_{hr15:92730505-92733423 24.556 1.148 0.317 3.624 2.903E-04 1.505E-02} _{chr3:99662724-99665668 43.178 0.778 0.215 3.623 2.913E-04 1.509E-02 MIR3921} _{chr20:58562257-58564416 27489 1527 0422 3622 2921E-04 1511E-02 CDH26} Attorney Docket No: 2014191-0041 c_{hr3:133245870-133247642 9.597 1.177 0.328 3.591 3.291E-04 1.621E-02 CDV3} _{chr8:22586460-22587173 9.787 0.852 0.237 3.591 3.291E-04 1.621E-02 EGR3} _{chr18:13425465-13426665 22228 0600 0167 3589 3325E-04 1634E-02 LDLRAD4-AS1} Attorney Docket No: 2014191-0041 c_{hr8:37017368-37018537 49.624 0.888 0.250 3.551 3.840E-04 1.782E-02} _{chr7:42907578-42912425 23.832 0.934 0.263 3.550 3.854E-04 1.786E-02 C7orf25} _{chr20:18400894-18402548 5528 1239 0349 3549 3863E-04 1789E-02 DZANK1} Attorney Docket No: 2014191-0041 c_{hr2:41668624-41670210 20.526 0.692 0.197 3.511 4.468E-04 1.965E-02} _{chr2:20063159-20063985 22.992 0.596 0.170 3.510 4.474E-04 1.966E-02 LINC00954} _{chr14:68979685-68982059 42344 0704 0201 3510 4484E-04 1969E-02} _L Attorney Docket No: 2014191-0041 c_{hr6:6927824-6928484 16.576 0.722 0.208 3.470 5.210E-04 2.165E-02} _{chr9:133029980-133033163 62.686 1.006 0.290 3.470 5.212E-04 2.165E-02} _{chr8:95507369-95508620 3400 1890 0545 3469 5218E-04 2166E-02 RAD54B} Attorney Docket No: 2014191-0041 c_{hr19:41449930-41452460 24.176 1.462 0.425 3.437 5.874E-04 2.340E-02 CYP2B7P} _{chr16:52594837-52596750 74.571 0.884 0.257 3.436 5.905E-04 2.348E-02 TOX3} _{chr20:19075731-19076812 20593 0723 0211 3436 5912E-04 2349E-02} _B Attorney Docket No: 2014191-0041 c_{hr1:177417147-177418685 15.265 1.261 0.371 3.397 6.815E-04 2.579E-02} _{chr2:45923968-45924806 5.242 1.107 0.326 3.397 6.810E-04 2.579E-02 PRKCE} _{chr21:41515435-41519322 31222 1119 0329 3397 6821E-04 2580E-02} _B Attorney Docket No: 2014191-0041 c_{hr8:36917591-36921777 24.109 1.731 0.513 3.373 7.430E-04 2.698E-02} _{chr5:54896110-54897671 18.307 0.811 0.240 3.372 7.467E-04 2.706E-02} _{chr3:120363144-120365860 33850 1110 0329 3372 7472E-04 2707E-02 HGD} Attorney Docket No: 2014191-0041 c_{hr14:89466256-89467687 10.496 1.037 0.310 3.345 8.234E-04 2.866E-02} _{chr10:114563667-114564940 23.493 0.710 0.212 3.344 8.248E-04 2.869E-02} _{chr8:118414134-118415591 17541 0816 0244 3344 8248E-04 2869E-02} ₁ Attorney Docket No: 2014191-0041 c_{hr22:43792512-43794350 26.773 0.882 0.266 3.313 9.225E-04 3.087E-02 MPPED1} _{chr12:119554986-119557294 30.462 0.772 0.233 3.313 9.237E-04 3.088E-02} _{chr22:43057700-43058990 16238 0966 0292 3312 9269E-04 3096E-02 CYB5R3} Attorney Docket No: 2014191-0041 c_{hr8:25623011-25624140 18.578 0.771 0.234 3.293 9.919E-04 3.220E-02} _{chr4:101014270-101015473 8.708 1.192 0.362 3.293 9.922E-04 3.220E-02} _{chr19:49370764-49372630 50170 0749 0227 3292 9947E-04 3224E-02 PLEKHA4} Attorney Docket No: 2014191-0041 c_{hr2:237982549-237983051 5.120 1.037 0.318 3.257 1.126E-03 3.487E-02 COPS8} _{chr3:12790901-12792455 37.095 0.644 0.198 3.257 1.128E-03 3.492E-02 TMEM40} _{chr16:74869044-74870829 11066 0716 0220 3256 1128E-03 3494E-02} Attorney Docket No: 2014191-0041 c_{hr12:67938251-67939432 11.531 0.610 0.189 3.229 1.243E-03 3.692E-02} _{chr6:134966037-134966332 2.982 1.224 0.379 3.229 1.244E-03 3.692E-02} _{chr20:55348424-55351877 25225 0758 0235 3227 1251E-03 3705E-02} Attorney Docket No: 2014191-0041 c_{hr22:29236110-29236333 4.171 1.023 0.320 3.199 1.380E-03 3.945E-02 XBP1} _{chr3:57787995-57790432 10.372 1.059 0.331 3.198 1.382E-03 3.949E-02 SLMAP} _{chr10:6408365-6409520 6607 0921 0288 3198 1383E-03 3950E-02} ₆ Attorney Docket No: 2014191-0041 c_{hr18:20843271-20843951 16.574 0.602 0.190 3.171 1.521E-03 4.183E-02} _{chr8:125816807-125817728 8.744 0.854 0.270 3.170 1.523E-03 4.186E-02} _{chr6:51393316-51394423 7322 0826 0260 3169 1527E-03 4193E-02} Attorney Docket No: 2014191-0041 c_{hr9:137598428-137601259 48.404 0.622 0.198 3.140 1.691E-03 4.469E-02} _{chr3:58372803-58374031 18.298 0.920 0.293 3.140 1.692E-03 4.470E-02 PXK} _{chr22:22895103-22897874 71953 0797 0254 3137 1708E-03 4496E-02 PRAME} Attorney Docket No: 2014191-0041 c_{hr14:93402462-93402819 9.155 0.824 0.265 3.108 1.882E-03 4.757E-02 CHGA} _{chr3:139631383-139631803 10.493 0.681 0.219 3.108 1.883E-03 4.757E-02 CLSTN2} _{chr8:126029068-126030544 22136 0654 0210 3108 1883E-03 4757E-02 SQLE} Attorney Docket No: 2014191-0041 c_{hr12:69846097-69847527 22.387 0.820 0.266 3.090 2.004E-03 4.936E-02 FRS2} _{chr4:40472785-40473935 7.696 0.807 0.261 3.090 2.004E-03 4.936E-02 MIR4802} _{chr2:132191519-132192482 6207 1445 0468 3089 2012E-03 4943E-02 NOC2LP2} ₂₀

Attorney Docket No: 2014191-0041 Table 6: Exemplary genomic loci that exhibit increased levels of H3K27ac modifications in cell lines deprived of exogenous estrogen as compared to cell lines cultured with exogenous estrogen. G_{enomic Loci baseMean log2FoldChange lfcSE stat pvalue padj Symbol} _{chr1:233522147-233524173 2.396 -3.6203 0.8194 -4.418 9.951E-06 1.448E-03 MAP3K21} _{h 14 7722 214 77 12 1 7 2 2 7 21 E 4 1241E 2 A NA1B} Attorney Docket No: 2014191-0041 c_{hr2:230802408-230803441 4.865 -2.3570 0.5656 -4.167 3.080E-05 3.354E-03 FBXO36} _{chr15:89066903-89067662 5.159 -2.3357 0.7067 -3.305 9.495E-04 3.142E-02 DET1} _{chr22:26565055-26566000 6625 -2 3336 05683 -4 106 4023E-05 4055E-03 SEZ6L} ₅ Attorney Docket No: 2014191-0041 c_{hr12:102482576-102483555 7.561 -2.1263 0.4978 -4.271 1.946E-05 2.359E-03 WASHC3} _{chr2:240142989-240145471 3.552 -2.1258 0.6524 -3.258 1.121E-03 3.478E-02 MGC16025} _{chr17:59825311-59826447 9152 -2 1258 06229 -3 413 6436E-04 2484E-02 BRIP1} Attorney Docket No: 2014191-0041 c_{hr8:140732169-140732727 4.025 -1.9688 0.4787 -4.113 3.903E-05 3.982E-03 KCNK9} _{chr1:226213741-226214436 7.919 -1.9664 0.4469 -4.401 1.080E-05 1.528E-03 SDE2} _{chr8:66496507-66497606 4652 -1 9627 05289 -3 711 2062E-04 1206E-02 LINC01299} Attorney Docket No: 2014191-0041 c_{hr21:46105261-46106516 5.081 -1.8446 0.4802 -3.841 1.225E-04 8.605E-03 KRTAP12-1} _{chr12:49035337-49036562 6.019 -1.8445 0.5154 -3.579 3.449E-04 1.671E-02 SNORA2C} _{chr1:198589681-198591536 4940 -1 8405 05747 -3 203 1362E-03 3914E-02 PTPRC} Attorney Docket No: 2014191-0041 c_{hr14:85999775-86000546 7.205 -1.7596 0.3877 -4.539 5.665E-06 9.560E-04 FLRT2} _{chr2:178709753-178710656 7.797 -1.7577 0.4860 -3.616 2.987E-04 1.534E-02 PDE11A} _{chr2:47381590-47382635 6155 -1 7555 03785 -4 638 3516E-06 6557E-04 STPG4} Attorney Docket No: 2014191-0041 c_{hr4:184932514-184935090 13.753 -1.6750 0.4044 -4.142 3.441E-05 3.621E-03 STOX2} _{chr12:110609981-110611228 10.243 -1.6740 0.4475 -3.741 1.832E-04 1.111E-02 IFT81} _{chr16:71458883-71460374 11809 -1 6737 04434 -3 775 1600E-04 1020E-02 ZNF23} _PAR Attorney Docket No: 2014191-0041 c_{hrX:37401063-37403165 16.674 -1.6154 0.3714 -4.349 1.366E-05 1.819E-03 LANCL3} _{chr1:240255236-240257158 44.977 -1.6134 0.4652 -3.468 5.239E-04 2.172E-02 FMN2} _{chr5:128308214-128309538 4671 -1 6126 04492 -3 590 3310E-04 1628E-02 SLC27A6} Attorney Docket No: 2014191-0041 c_{hr5:154010808-154011393 8.604 -1.5461 0.4778 -3.236 1.212E-03 3.641E-02 MIR3141} _{chr8:60030134-60033237 65.435 -1.5454 0.4568 -3.383 7.177E-04 2.651E-02 TOX} _{chr6:84954077-84955232 10512 -1 5447 04786 -3 228 1247E-03 3697E-02 CEP162} Attorney Docket No: 2014191-0041 c_{hr5:161087749-161088163 4.180 -1.5039 0.4308 -3.491 4.809E-04 2.057E-02 GABRA6} _{chr22:32636874-32637450 8.734 -1.5033 0.4355 -3.452 5.571E-04 2.258E-02 SLC5A4} _{chr7:19721324-19722170 5203 -1 5030 04558 -3 297 9767E-04 3187E-02 MIR3146} ₃ _X16 Attorney Docket No: 2014191-0041 c_{hr2:105866191-105868011 12.912 -1.4480 0.3619 -4.001 6.300E-05 5.445E-03 GPR45} _{chr17:36783175-36785987 20.497 -1.4479 0.3732 -3.879 1.048E-04 7.700E-03 SRCIN1} _{chr6:29942313-29943184 8680 -1 4468 04525 -3 198 1386E-03 3955E-02 HCG9} Attorney Docket No: 2014191-0041 c_{hr1:206495536-206495900 3.017 -1.3801 0.3844 -3.590 3.304E-04 1.626E-02 SRGAP2} _{chr14:71061282-71062391 5.457 -1.3798 0.3415 -4.040 5.350E-05 4.907E-03 MED6} _{chr2:54760399-54761162 4812 -1 3791 04450 -3 099 1942E-03 4836E-02 RPL23AP32} Attorney Docket No: 2014191-0041 c_{hr7:37802672-37803771 11.527 -1.3262 0.3372 -3.933 8.403E-05 6.633E-03 GPR141} _{chr12:111855978-111856791 15.993 -1.3261 0.3859 -3.437 5.893E-04 2.345E-02 SH2B3} _{chr10:132783803-132786490 7414 -1 3260 04168 -3 181 1466E-03 4088E-02 MIR378C} Attorney Docket No: 2014191-0041 c_{hr11:113934666-113935380 14.888 -1.2779 0.3469 -3.684 2.295E-04 1.293E-02 ZBTB16} _{chr3:100196321-100197709 45.338 -1.2774 0.2903 -4.400 1.082E-05 1.530E-03 TMEM45A} _{chr6:17745461-17746096 8449 -1 2772 03380 -3 778 1580E-04 1013E-02 KIF13A} ₂ Attorney Docket No: 2014191-0041 c_{hr1:214156075-214156902 19.773 -1.2482 0.3105 -4.020 5.825E-05 5.195E-03 PROX1} _{chr11:16631420-16632448 8.877 -1.2476 0.3300 -3.780 1.566E-04 1.007E-02 SOX6} _{chr1:168114586-168116292 10902 -1 2467 03799 -3 282 1032E-03 3306E-02 GPR161} _1P Attorney Docket No: 2014191-0041 c_{hr12:104099866-104100953 7.547 -1.2107 0.3142 -3.854 1.164E-04 8.310E-03 STAB2} _{chr10:1729928-1730858 8.434 -1.2097 0.3323 -3.641 2.716E-04 1.438E-02 ADARB2} _{chr6:3027765-3028286 10070 -1 2078 02957 -4 084 4429E-05 4305E-03 HTATSF1P2} _S1 _T Attorney Docket No: 2014191-0041 c_{hr15:76638359-76639831 63.267 -1.1790 0.2664 -4.426 9.601E-06 1.411E-03 SCAPER} _{chr2:29467397-29468768 73.671 -1.1778 0.3693 -3.189 1.428E-03 4.028E-02 ALK} _{chr7:72791668-72792083 6620 -1 1776 03784 -3 112 1860E-03 4728E-02 FKBP6} ₃ Attorney Docket No: 2014191-0041 c_{hr15:34714895-34716354 9.427 -1.1475 0.3217 -3.567 3.616E-04 1.721E-02 GOLGA8A} _{chr17:38153236-38155811 34.884 -1.1471 0.3272 -3.506 4.552E-04 1.988E-02 CSF3} _{chr11:43954405-43955621 19800 -1 1459 02667 -4 297 1729E-05 2153E-03 C11orf96} ₄ Attorney Docket No: 2014191-0041 c_{hr3:184388626-184389629 20.008 -1.1121 0.2980 -3.732 1.899E-04 1.134E-02 MAGEF1} _{chr21:28337591-28338743 15.038 -1.1115 0.3573 -3.111 1.867E-03 4.741E-02 ADAMTS5} _{chr3:15919425-15921676 11569 -1 1102 03086 -3 597 3219E-04 1602E-02 MIR563} Attorney Docket No: 2014191-0041 c_{hr9:115821876-115822484 6.903 -1.0803 0.3498 -3.089 2.009E-03 4.941E-02 ZFP37} _{chr5:136971898-136973241 8.518 -1.0803 0.3072 -3.516 4.375E-04 1.939E-02 MIR874} _{chr1:104130378-104131735 5202 -1 0801 03075 -3 513 4438E-04 1956E-02 AMY2B} ₁ Attorney Docket No: 2014191-0041 c_{hr8:41763439-41765457 28.395 -1.0456 0.3094 -3.379 7.273E-04 2.666E-02 ANK1} _{chr15:29246377-29247317 7.350 -1.0454 0.3224 -3.242 1.185E-03 3.594E-02 APBA2} _{chr13:55738799-55739980 9651 -1 0451 03157 -3 310 9316E-04 3107E-02 MIR5007} Attorney Docket No: 2014191-0041 c_{hr7:35191454-35192570 13.742 -1.0128 0.3109 -3.257 1.125E-03 3.486E-02 DPY19L2P1} _{chr10:124907085-124908383 24.357 -1.0127 0.3262 -3.104 1.909E-03 4.795E-02 HMX2} _{chr2:111148441-111148854 7011 -1 0125 02980 -3 397 6813E-04 2579E-02 LINC01123} ₀ Attorney Docket No: 2014191-0041 c_{hr5:93701933-93703211 27.948 -0.9809 0.2537 -3.866 1.105E-04 7.992E-03 KIAA0825} _{chrX:70895671-70896361 8.500 -0.9805 0.3139 -3.124 1.786E-03 4.620E-02 LINC00891} _{chr13:24077121-24078163 7635 -0 9796 02997 -3 268 1083E-03 3407E-02 LINC00327} Attorney Docket No: 2014191-0041 c_{hr2:47076942-47078319 11.944 -0.9566 0.2912 -3.285 1.022E-03 3.285E-02 LINC01119} _{chr19:45388773-45389431 13.465 -0.9565 0.2566 -3.728 1.931E-04 1.146E-02 TOMM40} _{chr5:35981915-35982550 6546 -0 9561 03101 -3 083 2050E-03 4991E-02 UGT3A1} ₉₂ Attorney Docket No: 2014191-0041 c_{hr16:58018415-58019980 51.020 -0.9298 0.2762 -3.366 7.632E-04 2.740E-02 TEPP} _{chr16:28845705-28847391 34.055 -0.9285 0.2390 -3.885 1.025E-04 7.588E-03 ATXN2L} _{chr11:13701935-13702250 6794 -0 9283 02493 -3 723 1965E-04 1162E-02 FAR1} Attorney Docket No: 2014191-0041 c_{hr12:110231964-110232291 7.109 -0.8995 0.2782 -3.234 1.222E-03 3.659E-02 TRPV4} _{chr1:161148781-161149552 21.225 -0.8995 0.2040 -4.409 1.039E-05 1.496E-03 B4GALT3} _{chr3:170081362-170082389 5687 -0 8987 02832 -3 174 1503E-03 4153E-02 SKIL} Attorney Docket No: 2014191-0041 c_{hr5:31775615-31777607 36.435 -0.8750 0.2762 -3.169 1.532E-03 4.199E-02 PDZD2} _{chr6:51910812-51913529 19.030 -0.8741 0.2377 -3.677 2.357E-04 1.315E-02 PKHD1} _{chr19:4094530-4095641 11070 -0 8741 02755 -3 173 1510E-03 4165E-02 MAP2K2} ₂ Attorney Docket No: 2014191-0041 c_{hr10:133988968-133990071 9.629 -0.8427 0.2637 -3.196 1.395E-03 3.972E-02 JAKMIP3} _{chr1:196835878-196838604 17.051 -0.8423 0.2370 -3.554 3.791E-04 1.767E-02 CFHR4} _{chr1:227081467-227083717 23988 -0 8418 02115 -3 981 6869E-05 5802E-03 COQ8A} _S4 Attorney Docket No: 2014191-0041 c_{hr2:173577209-173578663 15.570 -0.8170 0.2290 -3.567 3.612E-04 1.720E-02 RAPGEF4} _{chr3:123396229-123397514 15.749 -0.8151 0.2574 -3.166 1.545E-03 4.226E-02 MYLK} _{chr8:99412040-99412827 11385 -0 8151 02464 -3 308 9389E-04 3120E-02 KCNS2} ₂ Attorney Docket No: 2014191-0041 c_{hr6:25678699-25680931 26.087 -0.7839 0.2341 -3.348 8.131E-04 2.845E-02 SCGN} _{chr1:3417877-3419370 28.899 -0.7838 0.1972 -3.976 7.021E-05 5.890E-03 MEGF6} _{chr5:70872598-70874640 24879 -0 7824 01951 -4 011 6052E-05 5292E-03 MCCC2} Attorney Docket No: 2014191-0041 c_{hr5:119786757-119787445 7.640 -0.7521 0.2316 -3.248 1.164E-03 3.559E-02 PRR16} _{chr3:44992953-44995427 18.994 -0.7521 0.1975 -3.809 1.397E-04 9.429E-03 ZDHHC3} _{chr10:43248412-43251169 68780 -0 7517 02296 -3 274 1060E-03 3360E-02 BMS1} Attorney Docket No: 2014191-0041 c_{hr2:95420797-95422915 32.349 -0.7123 0.2065 -3.449 5.626E-04 2.274E-02 FAM95A} _{chr10:94838928-94841286 19.084 -0.7123 0.2076 -3.431 6.014E-04 2.375E-02 CYP26A1} _{chr20:34379599-34381896 113945 -0 7109 01799 -3 951 7769E-05 6304E-03 PHF20} Attorney Docket No: 2014191-0041 c_{hr2:28711481-28713286 14.285 -0.6749 0.2132 -3.165 1.551E-03 4.236E-02 PLB1} _{chr10:49930208-49931040 11.954 -0.6740 0.2040 -3.304 9.537E-04 3.150E-02 WDFY4} _{chr10:103606049-103607757 13396 -0 6736 02116 -3 183 1456E-03 4071E-02 KCNIP2} ₃ Attorney Docket No: 2014191-0041 c_{hr2:1825485-1827224 18.701 -0.6389 0.1687 -3.786 1.528E-04 9.959E-03 MYT1L} _{chr1:154791526-154793133 20.824 -0.6377 0.2035 -3.133 1.728E-03 4.526E-02 KCNN3} _{chr22:43506060-43508015 113916 -0 6376 01613 -3 952 7758E-05 6300E-03 BIK} Attorney Docket No: 2014191-0041 c_{hr17:57947805-57949375 36.227 -0.5960 0.1754 -3.398 6.794E-04 2.576E-02 TUBD1} _{chr12:88207067-88208467 26.400 -0.5931 0.1622 -3.657 2.552E-04 1.386E-02 MKRN9P} _{chr2:11505216-11505953 11335 -0 5920 01855 -3 191 1418E-03 4008E-02 ROCK2}

Attorney Docket No: 2014191-0041 Table 7: Exemplary genes associated with enhancer loci that (i) exhibit increased levels of H3K27ac modifications in cell lines cultured with exogenous estrogen as compared to cell lines deprived of exogenous estrogen, (ii) are in close proximity (within 2,000 kB) of a ER-binding site, (iii) are in proximity to a gene that has previously been shown to be repressed in tamoxifen resistant cancers, and (iv) are not in close proximity (not within 2,000 kB) of a FOXA1 binding site previously shown to be associated with tamoxifen resistance. _{CELSR2 ZNF32 SNX19 ZNF516 BOD1} _{PGR KCNMA1 PTPRO ZNF236 PRAG1}

Attorney Docket No: 2014191-0041 Table 8: Exemplary genes associated with enhancer loci that (i) exhibit increased levels of H3K27ac modifications in cell lines deprived of exogenous estrogen as compared to cell lines cultured with exogenous estrogen, and (ii) are in close proximity (within 2,000 kB) of a FOXA1 binding site previously shown to be associated with tamoxifen resistance. _{FGFR2 BROX GPRC5D DAOA BMERB1 EHD2 PLCB4 CCK SLIT3 OPRK1} _{KLF5 TAF5L C12orf40 EFNB2 NDE1 KCNS3 CBFA2T2 CCDC54 SLC22A23 ATP6V1H}

Attorney Docket No: 2014191-0041 Table 9: Exemplary genomic loci that (i) exhibit increased levels of H3K27ac modifications in cell lines cultured with exogenous estrogen as compared to cell lines deprived of exogenous estrogen, (ii) are in close proximity (within 2,000 kB) of a ER-binding site, (iii) are in proximity to a gene that has previously been shown to be repressed in tamoxifen resistant cancers, and (iv) are not in close proximity (not within 2,000 kB) of a FOXA1 binding site previously shown to be associated with tamoxifen resistance. _{chr1:7528934-7534233 chr14:67926961-67930160} _{chr1:109788415-109791814 chr14:75859130-75860529}

Attorney Docket No: 2014191-0041 Table 10: Exemplary genomic loci shown to (i) exhibit increased levels of H3K27ac modifications in cell lines deprived of estrogen as compared to cell lines cultured with exogenous estrogen, and (ii) which are in close proximity (within 2,000 kB) of a FOXA1 binding site previously shown to be associated with tamoxifen resistance. _{chr1:8073184-8085783 chr13:20417398-20418697 chr2:216793991-216795900 chr5:127216099-127223798} _{chr1:18526886-18530285 chr13:74351844-74353843 chr2:233158941-233168540 chr5:128230977-128232776} Attorney Docket No: 2014191-0041 OTHER EMBODIMENTS [0434] It will be appreciated that the scope of the present disclosure is to be defined by that which may be understood from the disclosure and claims rather than by the specific embodiments that have been presented by way of example. Elements described with respect to one aspect or embodiment of the present disclosure are also contemplated with respect to other aspects or embodiments of the present disclosure. For example, elements of claims that depend directly or indirectly from a certain independent claim presented herein serve as support for those elements being presented in additional dependent claims of one or more other independent claims. Throughout the description, where compositions or methods are described as having, including, or comprising specific elements, it is to be understood that compositions or methods that consist essentially of, consist of, or do not comprise the recited elements are likewise hereby disclosed. All references cited herein are hereby incorporated by reference.

Claims

Attorney Docket No: 2014191-0041 CLAIMS What is claimed is: 1. A method of measuring estrogen receptor (ER) pathway activity of a cancer in a subject, the method comprising: quantifying, at one or more genomic loci in a biological sample, optionally in cell-free DNA (cfDNA) from a liquid biopsy sample, obtained or derived from the subject: (i) one or more histone modifications, (ii) chromatin accessibility, (iii) binding of one or more transcription factors, and/or (iv) DNA methylation.

2. The method of claim 1, wherein the one or more histone modifications are quantified using a histone modification assay that measures one or more of H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac, H3K4me1, H3K4me2, H3K4me3, and pan-acetylation.

3. The method of claim 2, wherein the histone modification assay detects H3K4me3 modifications.

4. The method of claim 2, wherein the histone modification assay detects H3K27ac modifications.

5. The method of any one of claims 2-4, wherein the histone modification assay is selected from ChIP-seq (Chromatin ImmunoPrecipitation sequencing), CUT&RUN (Cleavage Under Targets and Release Using Nuclease) sequencing, and CUT&Tag (Cleavage Under Targets and Tagmentation) sequencing. Attorney Docket No: 2014191-0041

6. The method of any one of claims 1-5, wherein chromatin accessibility is quantified using ATAC-seq (Assay of Transpose Accessible Chromatin sequencing), NOMe-seq (Nucleosome Occupancy and Methylome sequencing), FAIRE-seq (Formaldehyde-Assisted Isolation of Regulatory Elements sequencing), MNase-seq (Micrococcal Nuclease digestion with sequencing), a DNase hypersensitivity assay, or a fragmentomics assay.

7. The method of any one of claims 1-6, wherein the binding of one or more transcription factors is quantified using a transcription factor binding assay that detects binding of p300, mediator complex, cohesion complex, RNA pol II, FOXA1, ESR1, PR, MYC, EN1, FOXM1, KLF4, AP-2, RARa, RUNX1, ER, or any combination thereof.

8. The method of claim 7, wherein the transcription factor binding assay is ChIP-seq (Chromatin ImmunoPrecipitation sequencing), CUT&RUN (Cleavage Under Targets and Release Using Nuclease) sequencing, or CUT&Tag (Cleavage Under Targets and Tagmentation) sequencing.

9. The method of any one of claims 1-8, wherein DNA methylation is quantified using Bisulfite sequencing (BS-Seq), Whole Genome Bisulfite Sequencing (WGBS), Methylated DNA ImmunoPrecipitation sequencing (MeDIP-seq), or Methyl-CpG-Binding Domain sequencing (MBD-seq).

10. The method of any one of claims 1-9, comprising quantifying two or more of the following, each at one or more genomic loci in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from the subject: (i) one or more histone modifications, (ii) chromatin accessibility, (iii) transcription factor binding, and/or (iv) DNA methylation.

11. The method of any one of claims 1-10, comprising quantifying two or more histone modifications. Attorney Docket No: 2014191-0041

12. The method of claim 11, comprising quantifying H3K4me3 and H3K27ac modifications. 13. The method of any one of claims 1-12, wherein the genomic loci are characterized in that they exhibit increased signal in: (i) an ER+ cancer (e.g., one or more samples obtained from one or more subjects having an ER+ cancer) as compared to an ER- cancer (e.g., one or more samples obtained from one or more subjects having an ER+ cancer); (ii) an mESR1 cancer (e.g., one or more samples obtained from one or more subjects having an mESR1 cancer) as compared to a cancer without an mESR1 mutation (e.g., one or more samples obtained from one or more subjects not having an mESR1 cancer); and/or (iii) one or more ER+ cancer cell lines incubated with exogenous estrogen as compared to one or more ER+ cancer cell lines not incubated with exogenous estrogen and/or one or more ER- cancer cell lines. 14. The method of any one of claims 1-13, comprising quantifying: (i) one or more histone modifications at one or more regulatory regions (e.g., promoter or enhancer regions) associated with one or more genes listed in Tables 1-8, (ii) chromatin accessibility at one or more of the genes listed in Tables 1-8, (iii) binding of one or more transcription factors associated with activation and/or repression of the estrogen receptor signaling pathway (e.g., transcription factors associated with promoting or repressing expression of one or more of the genes listed in Tables 1-8), and/or (iv) DNA methylation of one or more of the genes listed in Tables 1-8. 15. The method of claim 14, comprising quantifying promoter signal and/or enhancer signal associated with one or more of the genes listed in Tables 1-8 (e.g., quantifying promoter signal at one or more of the promoter loci listed in Table 1, 3, or 4 and/or quantifying enhancer signal at one or more of the enhancer loci listed in Table 2, 5, 6, 9 or 10). Attorney Docket No: 2014191-0041 16. The method of claim 14 or 15, comprising quantifying promoter signal at a promoter of one or more genes induced by ER pathway activation (e.g., quantifying promoter signal at one or more of the induced promoter loci listed in Table 1 or 3). 17. The method of any one of claims 14-16, comprising quantifying enhancer signal at one or more enhancer regions associated with one or more genes induced by ER pathway activation (e.g., quantifying enhancer signal at one or more of the induced enhancer loci listed in Table 2, 5, or 9). 18. The method of claim 16 or 17, wherein the one or more genes induced by ER pathway activation comprise 5, 6, or 7 of the induced genes listed in any one of Tables 1-8 (e.g., AMZ1, CELSR2, FKBP4, GREB1, OLFM1, SLC9A3R1, or TFF1, or any combination thereof). 19. The method of claim 16 or 17, wherein the one or more genes induced by ER pathway activation comprise 5, 6, 7, 8, 9, or 10 of the induced genes listed in any one of Tables 1-8 (e.g., AMZ1, AREG, CELSR2, FKBP4, FMN1, GREB1, OLFM1, RBM24, SLC9A3R1, or TFF1, or any combination thereof). 20. The method of claim 16 or 17, wherein the one or more genes induced by ER pathway activation comprise 5, 6, 7, 8, 9, 10, 11, 12,

13,

14,

15,

16,

17,

18,

19,

20, or 21 of the induced genes listed in any one of Tables 1-8 (e.g., AMZ1, AREG, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, or ZNF703, or any combination thereof).

21. The method of any one of claims 14-20, wherein the method comprises: (i) summing promoter signal at two or more of the induced promoter loci listed in Table 1, 3, or 4; (ii) summing enhancer signal at two or more of the induced enhancer loci listed in Table 2, 5, 6, 9, or 10; (iii) summing promoter signal at two or more of the repressed promoter loci listed in Table 1; Attorney Docket No: 2014191-0041 (iv) summing enhancer signal at two or more repressed enhancer loci listed in Table 2; or (v) any combination of (i)-(iv).

22. The method of claim 21, wherein promoter signal comprises a measure of H3K4me3 modifications, and/or wherein enhancer signal comprises a measure of H3K27ac modifications.

23. A method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining a promoter score for the sample, wherein the promoter score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the induced promoter loci listed in Table 1, (ii) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the repressed promoter loci listed in Table 1, (iii) dividing the result of (i) by the result of (ii).

24. A method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining an enhancer score for the sample, wherein the enhancer score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the induced enhancer loci listed in Table 2, (ii) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the repressed enhancer loci listed in Table 2, and (iii) dividing the result of (i) by the result of (ii).

25. A method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; Attorney Docket No: 2014191-0041 determining an ER-induced score for the sample, wherein the ER-induced score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the induced promoter loci listed in Table 1, (ii) combining (e.g., summing, averaging, geometric mean averaging) enhancer signal at one or more of the induced enhancer loci listed in Table 2, and (iii) combining (e.g., adding) the result of (i) and (ii).

26. A method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; determining an ER pathway activity score for the sample, wherein the ER pathway activity score is determined by a method comprising combining (e.g., summing) a promoter score and an enhancer score, wherein: (a) the promoter score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the induced promoter loci listed in Table 1, (ii) combining (e.g., summing, averaging, or geometric mean averaging) promoter signal at one or more of the repressed promoter loci listed in Table 1, (iii) dividing the result of (a)(i) by the result of (a)(ii); and (b) the enhancer score is determined by a method comprising: (i) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the induced enhancer loci listed in Table 2, (ii) combining (e.g., summing, averaging, or geometric mean averaging) enhancer signal at one or more of the repressed enhancer loci listed in Table 2, and (iii) dividing the result of (b)(i) by the result of (b)(ii).

27. The method of claim 25 or 26, wherein the promoter score and the enhancer score are scaled prior to combining such that the maximum and minimum enhancer signal scores have the same value as the maximum and minimum promoter scores (e.g., to provide values between 0 and 1). Attorney Docket No: 2014191-0041

28. The method of any one of claims 26 or 27, wherein ER activity is corrected for ctDNA%.

29. The method of any one of claims 23-28, wherein the one or more induced promoter loci comprise 5, 6, or 7 of the promoter regions of induced genes listed in Table 1 (including, e.g., AMZ1, CELSR2, FKBP4, GREB1, OLFM1, SLC9A3R1, or TFF1 or any combination thereof).

30. The method of any one of claims 23-29, wherein the one or more induced promoter loci comprise 5, 6, 7, 8, 9, or 10 of the promoter regions of induced genes listed in Table 1 (e.g., AMZ1, AREG, CELSR2, FKBP4, FMN1, GREB1, OLFM1, RBM24, SLC9A3R1, or TFF1, or any combination thereof).

31. The method of any one of claims 23-30, wherein the one or more induced promoter loci comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the promoter regions of induced genes listed in Table 1 (e.g., AMZ1, AREG, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, or ZNF703, or any combination thereof).

32. The method of any one of claims 23-31, wherein the one or more induced enhancer loci comprise one or more enhancer regions associated with 5, 6, or 7 of the induced genes listed in Table 1 (including, e.g., AMZ1, CELSR2, FKBP4, GREB1, OLFM1, SLC9A3R1, or TFF1, or any combination thereof).

33. The method of any one of claims 23-32, wherein the one or more induced enhancer loci comprise one or more enhancer regions associated with 5, 6, 7, 8, 9, or 10 of the promoter regions of induced genes listed in Table 1 (e.g., AMZ1, AREG, CELSR2, FKBP4, FMN1, GREB1, OLFM1, RBM24, SLC9A3R1, or TFF1, or any combination thereof). Attorney Docket No: 2014191-0041

34. The method of any one of claims 23-33, wherein the one or more induced enhancer loci comprise one or more enhancer regions associated with 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of the enhancer regions of induced genes listed in Table 1 (e.g., AMZ1, AREG, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, or ZNF703, or any combination thereof).

35. The method of any one of claims 23-34, wherein the one or more repressed promoter loci comprise 5, 6, or 7 of the promoter regions of repressed genes listed in Table 1.

36. The method of any one of claims 23-35, wherein the one or more repressed promoter loci comprise 5, 6, 7, 8, 9, or 10 of the promoter regions of repressed genes listed in Table 1.

37. The method of any one of claims 23-36, wherein the one or more repressed promoter loci comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 of the promoter regions of repressed genes listed in Table 1.

38. The method of any one of claims 23-37, wherein the one or more repressed enhancer loci comprise one or more enhancer regions associated with 5, 6, or 7 of the repressed genes listed in Table 2.

39. The method of any one of claims 23-38, wherein the one or more repressed enhancer loci comprise one or more enhancer regions associated with 5, 6, 7, 8, 9, or 10 of the repressed genes listed in Table 2.

40. The method of any one of claims 23-39, wherein the one or more repressed enhancer loci comprise one or more enhancer regions associated with 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 of the repressed genes listed in Table 2. Attorney Docket No: 2014191-0041

41. The method of any one of claims 23-40, wherein the method comprises quantifying H3K4me3 modifications for at least 5, 10, 20, or 30 or more of the genomic promoter loci listed in Table 1.

42. The method of any one of claims 23-41, wherein promoter signal comprises a measure of H3K4me3 modifications, and/or wherein enhancer signal comprises a measure of H3K27ac modifications.

43. The method of any one of claims 23-42, wherein the method comprises quantifying H3K27ac modifications for at least 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 2.

44. A method of measuring ER pathway activity of a cancer in a subject, comprising: obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; and measuring ER pathway activity for the sample, wherein ER pathway activity is measured using a method that comprises measuring levels of enhancer signal or promoter signal in the cfDNA at one or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal in one or more cell lines (e.g., ER+ breast cancer cell lines) treated with exogenous estrogen as compared to one or more cell lines (e.g., ER+ breast cancer cell lines) not treated with exogenous estrogen and/or one or more cell lines (e.g., ER+ breast cancer cell lines) deprived of estrogen.

45. The method of claim 44, wherein the one or more loci that have been shown to exhibit increased levels of promoter signal in one or more cell lines include at least 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 3.

46. The method of claim 44 or 45, wherein the one or more loci that have been shown to exhibit increased levels of enhancer signal in one or more cell lines include at least 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 5. Attorney Docket No: 2014191-0041

47. The method of any one of claims 44-46, wherein the method comprises measuring enhancer signal only at the one or more genomic loci that have been shown to exhibit increased levels of enhancer signal and that are: (i) within 10,000 bp (e.g., 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 kp) of an ER binding site; (ii) within 500,000 bp (e.g., within 400,000; 300,000; 200,000; 150,000; 100,000; or 50,000 bp) of a gene that is repressed in a cancer that is resistant to treatment with ER-targeted therapies; (iii) not within 10,000 bp (e.g., 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 bp) of a FOXA1 binding site associated with resistance to tamoxifen; or (iv) any combination of (i)-(iii).

48. The method of any one of claims 44-47, wherein the one or more genomic loci that have been shown to exhibit increased levels of enhancer signal comprise one of more genomic loci within an enhancer region of at least 1, 5, 10, 15, 20, 25, 30, 35, 40, or 50 of the genes listed in Table 7.

49. The method of claim 48, wherein the one or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal comprise at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 9.

50. The method of any one of claims 44-49, wherein the method comprises measuring enhancer signal or promoter signal at two or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal, and combining (e.g., summing, averaging (including, e.g., geometric mean averaging and/or weighted sum averaging) the enhancer signal or promoter signal measured at the two or more genomic loci.

51. The method of any one of claims 44-50, wherein the method further comprises determining enhancer signal or promoter signal at: Attorney Docket No: 2014191-0041 (a) one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer (e.g., ER+ breast cancer) cell lines deprived of exogenous estrogen as compared to the same cancer cell lines cultured with incubated with media comprising exogenous estrogen; and/or (b) one or more genomic loci that are in close proximity (e.g., loci within 10,000, 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 bp) to a FOXA1 binding site associated with resistance to tamoxifen.

52. The method of claim 51, wherein the method comprises combining (e.g., summing, or averaging (including, e.g., weighted sum averaging and/or geometric mean averaging)) enhancer and/or promoter signal measured at (a) the one or more genomic loci shown to exhibit increased enhancer signal or promoter signal in cancer cell lines deprived of exogenous estrogen; and/or (b) the one or more genomic loci that are in close proximity to a FOXA1 binding site associated with resistance to tamoxifen.

53. The method of claim 52, wherein the method comprises adjusting the combined enhancer signal or promoter signal measured at two or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal in cell lines incubated with media comprising exogenous estrogen as compared to cell lines not incubated with exogenous estrogen and/or deprived of exogenous estrogen with the combined enhancer and promoter signal measured at (a) the one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer cell lines deprived of exogenous estrogen; and/or (b) the one or more genomic loci that are in close proximity to a FOXA1 binding site associated with resistance to tamoxifen.

54. The method of claim 53, wherein the method comprises subtracting the combined enhancer and promoter signal measured at (a) the one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer cell lines deprived of exogenous estrogen; and (b) the one or more genomic loci that are in close proximity to a FOXA1 binding site associated with resistance to tamoxifen Attorney Docket No: 2014191-0041 from the combined enhancer signal or promoter signal measured at two or more genomic loci that have been shown to exhibit increased levels of enhancer signal or promoter signal in cell lines incubated with media comprising exogenous estrogen as compared to cell lines not incubated with exogenous estrogen and/or deprived of exogenous estrogen.

55. The method of any one claims 14-54, wherein enhancer signal and/or promoter signal in the liquid biopsy sample is measured using a method that comprises sequencing cfDNA comprising one or more histone modifications (e.g., H3K4me3 and/or H3K27ac), e.g., using cfChIP-seq, and wherein enhancer signal and/or promoter signal is a function of the number of sequence reads that overlap the one or more genomic loci.

56. The method of claim 55, wherein the sequence reads at each genomic loci are processed prior to combining with sequence reads at other genomic loci (e.g., quantile normalized and/or adjusted for background signal.

57. The method of any one of claims 1-56, wherein the genomic loci are characterized in that they exhibit low signal in healthy patient samples, and/or are regions at which signal of one or more epigenetic modification is correlated with ctDNA% (e.g., estimated ctDNA%).

58. The method of any one of claims 1-57, wherein each the genomic loci are characterized in that they exhibit increased signal in: (i) an ER+ cancer (e.g., one or more samples obtained from one or more subjects having an ER+ cancer) as compared to an ER- cancer (e.g., one or more samples obtained from one or more subjects having an ER+ cancer); (ii) an mESR1 cancer (e.g., one or more samples obtained from one or more subjects having an mESR1 cancer) as compared to a cancer without an mESR1 mutation (e.g., one or more samples obtained from one or more subjects not having an mESR1 cancer); and/or (iii) one or more ER+ cancer cell lines incubated with exogenous estrogen as compared to one or more ER+ cancer cell lines not incubated with exogenous estrogen and/or one or more ER- cancer cell lines. Attorney Docket No: 2014191-0041

59. The method of claim 58, wherein each of the genomic loci are characterized in that the signal is increased by an absolute log2(fold-change) of at least 2.0 (e.g., at least 2.5, at least 3.0, at least 3.5, or at least 4.0).

60. The method of any one of claims 1-59, wherein the liquid biopsy sample is a plasma sample, serum sample, or urine sample.

61. A method of determining whether a cancer in a subject is ER-positive or ER-negative, comprising: (i) obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; and (ii) measuring ER pathway activity (e.g., determining an ER activity score using a method of any one of claims 26-44) in the biological sample, wherein the ER pathway activity is determined by a method of any one of claims 23-60, wherein the cancer is determined to be ER-positive if the ER pathway activity score is greater than or equal to a threshold value, and the cancer is determined to be ER-negative if the ER pathway activity score is less than the threshold value.

62. A method of treating a subject having cancer, a method of predicting a subject having cancer’s responsiveness to an ER-targeted agent, a method of predicting a subject having cancer’s susceptibility to treatment with an ER-targeted agent, or a method of predicting a subject having cancer’s resistance to treatment with an ER-targeted agent, comprising measuring ER pathway activity using the method of any one of claims 1-61.

63. A method of treating a subject having a cancer, the method comprising: administering an ER-targeted agent to the subject if the cancer is determined to be ER- positive, and not administering a cancer therapy if the cancer is determined to be ER-negative, wherein the cancer is determined to be ER-positive or ER-negative using the method of claim 61. Attorney Docket No: 2014191-0041

64. A method of treating a subject having a cancer, the method comprising: (i) obtaining a biological sample comprising cell-free DNA (cfDNA), optionally a liquid biopsy sample, from the subject; (ii) determining ER pathway activity (e.g., determining an ER activity score using a method of any one of claims 26-44) in the biological sample, wherein the ER activity is determined using a method of any one of claims 23-60; and (iii) administering an ER-targeted agent to the subject if the ER pathway activity is greater than or equal to reference value (e.g., a threshold value), and not administering an ER- targeted agent to the subject if the ER pathway activity is less than the reference value (e.g., threshold value).

65. The method of any one of claims 59-64, wherein the reference value (e.g., threshold value) is a predetermined threshold value and/or a normalized value.

66. The method of any one of claims 61-65, wherein the reference value (e.g., threshold value) is an ER pathway activity measurement (e.g., an ER pathway activity score) determined in a reference population.

67. The method of claim 66, wherein the reference population comprises subjects having cancer and previously found to respond to treatment with an ER-targeted agent.

68. The method of claim 66, wherein the reference population comprises subjects having cancer and previously found to not respond to treatment with an ER-targeted therapy, and wherein the threshold value is greater than the ER activity score determined in the reference population.

69. The method of any one of claims 66-68, wherein the reference population comprises subjects having an ER-positive cancer (e.g., as determined by IHC). Attorney Docket No: 2014191-0041

70. The method of any one of claims 66-69, wherein the reference is the lower bound of the bottom quintile, the lower bound of the top quartile, the lower bound of the top tertile, the median, the lower bound of the fourth quintile, the lower bound of the top tertile, the lower bound of the quartile, or the lower bound of the top quintile of ER pathway activity values determined in the reference population.

71. The method of any one of claims 66-70, wherein the reference population comprises subjects having an ER-negative cancer (e.g., as determined by IHC) or determined to be cancer free, and wherein the reference value (e.g., threshold value) is greater than the ER activity score determined in the reference population.

72. The method of any one of claims 64-71, wherein an ER targeted agent is administered to the subject if the ER pathway activity score is between about 0.25 and about 2.00, about 0.30 and about 2.00, about 0.35 and about 2.00, about 0.40 and about 2.00, about 0.45 and about 2.00, about 0.50 and about 2.00, about 0.55 and about 2.00, or about 0.60 and about 2.00.

73. A method of monitoring cancer (e.g., ER-positive cancer) in a subject, and optionally treating the cancer, the method comprising: measuring ER pathway activity of the cancer using the method of any one of claims 1-60 at a first and a second time point.

74. The method of claim 73, wherein the subject has been administered an ER-targeted agent at or prior to the first time point or after the first time point and before the second time point.

75. The method of claim 73 or 74, comprising administering an ER-targeted agent to the subject based on the change in ER pathway activity between the first time point and the second time point, optionally wherein the type, dose, and/or frequency of administration of the ER- targeted therapy is adjusted based on the change in ER pathway activity. Attorney Docket No: 2014191-0041

76. The method of any one of claims 73-75, wherein the subject has an improved probability of responding to the ER-targeted agent if ER pathway activity decreases between the first time point and the second time point.

77. The method of claim 76, comprising continuing to administer the ER-targeted agent (e.g., administering one or more additional doses of the ER-targeted therapy) if the ER pathway activity increases or stays approximately the same between the first time point and the second time point.

78. The method of any one of claims 73-77, wherein, if the ER pathway activity decreases, the method comprises increasing the amount of ER-targeted agent administered to the subject and/or the frequency at which the ER-targeted agent is administered to the subject; or administering a different ER-targeted agent to the subject or administering a therapy that does not comprise administering an ER-targeted agent (e.g., a therapy for treatment of an ER- negative cancer).

79. The method of any one of claims 73-78, wherein the method comprises determining enhancer and/or promoter signal at: (a) one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer (e.g., ER+ breast cancer) cell lines deprived of exogenous estrogen; and/or (b) one or more genomic loci that are in close proximity (e.g., loci within 10,000; 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, or 2,000 bp) to a FOXA1 binding site associated with resistance to tamoxifen; and, if enhancer and/or promoter signal is increased at the one or more genomic loci of (a) and/or (b), administering a therapy that does not comprise an ER-targeted agent, and, if enhancer or promoter signal is constant or decreases at the one or more genomic loci of (a) and/or (b), continuing to administer an ER-targeted agent. Attorney Docket No: 2014191-0041

80. The method of claim 79, wherein the method comprises combining (e.g., summing, averaging (including, e.g., weighted sum averaging and/or geometric mean averaging) enhancer or promoter signal measured at (a) the one or more genomic loci that have been shown to exhibit increased enhancer or promoter signal in cancer cell lines deprived of exogenous estrogen; and (b) the one or more genomic loci that are in close proximity to a FOXA1 binding site associated with resistance to tamoxifen; and if the combined enhancer or promoter signal increases between the first time point and the second time point, ceasing administering the ER-targeted agent; and if the combined enhancer or promoter signal decreases or stays approximately the same between the first time point and the second time point, continuing to administer the ER-targeted agent.

81. The method of any one of claims 1-80, wherein the subject has previously been determined to have the cancer.

82. The method of any one of claims 1-81, wherein the cancer is breast cancer, ovarian cancer, or endometrial cancer.

83. The method of any one of claims 1-81, wherein the cancer is breast cancer, optionally wherein the cancer is ER+ breast cancer (e.g., as determined using IHC).

84. The method of any one of claims 1-83, wherein the subject is a human.

85. A method for testing the ER-targeting activity of a compound, comprising incubating the compound with a cell line, measuring ER pathway activity in the cell line subsequent to incubating the cell line with the compound, wherein the ER pathway activity is measured using the method of any one of claims 1-60, except that a cell line is used in place of a biological sample of a subject. Attorney Docket No: 2014191-0041

86. The method of claim 85, wherein the ER pathway activity measured subsequent to incubating with the compound is measured using a method of any one of claims 26-59, except that a cell line is used in place of a biological sample.

87. The method of claim 85 or 86, where the cell line has measurable ER pathway activity (e.g., the cell line has been incubated with a composition that increases ER signaling activity (e.g., estrogen or a derivative thereof)) prior to incubating with the compound.

88. The method of any one of claims 85-87, wherein the cell line is a cancer cell line, a breast cancer cell line, an ER+ cancer cell line, or an ER+ breast cancer cell line.

89. The method of any one of any one of claims 85-88, wherein the method comprises: (i) comparing the measured ER pathway activity to an ER pathway activity measured in a cell line not incubated with the compound, wherein the ER pathway activity of the cell line not incubated with the compound has been measured using the method of any one of claims 1-59, except that the cell line was used in place of a biological sample of a subject, and optionally wherein the cell line incubated with the compound and the cell line not incubated with the compound are the same cell line; and/or (ii) comparing the measured ER pathway to an ER pathway activity measured in a cell line deprived of exogenous estrogen, optionally wherein (i) the cell line deprived of exogenous estrogen has also been incubated with the compound before and/or after estrogen deprivation and/or (ii) the two cell lines are the same cell line.

90. The method of claim 89, where the cell line not incubated with the compound has measurable ER pathway activity, (e.g., wherein has been incubated with a composition that increases ER signaling activity (e.g., estrogen or a derivative thereof)).

91. The method of claim 89 or 90, wherein the cell line not incubated with the compound and/or the cell line deprived of exogenous estrogen is a cancer cell line, a breast cancer cell line, an ER+ cancer cell line, or an ER+ breast cancer cell line. Attorney Docket No: 2014191-0041

92. A method of screening a library of compounds for ER-targeting activity, comprising testing the activity of each compound using the method of any one of claims 85-91.

93. A compound identified by the method of any one of claims 85-82.

94. A kit comprising reagents for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci, wherein the one or more genomic loci are selected from those listed in Table 1, 2, 3, 4, 5, 6, 9, or 10.

95. The kit of claim 94, wherein the kit comprises reagents for quantifying H3K4me3 for: (a) at least 1, 5, 10, 20, 30, or 38 genomic loci listed in Table 1; (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 3; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 4; or (d) any combination of (a)-(c).

96. The kit of claim 94 or 95, wherein the kit comprises reagents for quantifying H3K27ac for: (a) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 2. (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 5; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 6; (d) at least 1, 5, 10, 20, 30, or 40 genomic loci listed in Table 9; (e) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 10; or (f) any combination of (a)-(e).

97. The kit of any one of claims 94-96, wherein the kit comprises one or more antibodies for use in ChIP-seq, optionally wherein the one or more antibodies specifically bind H3K4me3- or H3K27ac-modified histones.

98. The kit of any one of claims 94-97, wherein the kit comprises reagents for isolation of cell-free DNA (cfDNA) from a liquid biopsy sample. Attorney Docket No: 2014191-0041

99. The kit of any one of claims 94-98, wherein the kit comprises reagents for library preparation for sequencing.

100. The kit of any one of claims 94-99, wherein the kit comprises reagents for sequencing.

101. A non-transitory computer readable storage medium encoded with a computer program, wherein the program comprises instructions that when executed by one or more processors cause the one or more processors to perform operations to perform the method of any one of claims 1- 100.

102. A computer system comprising a memory and one or more processors coupled to the memory, wherein the one or more processors are configured to perform operations to perform the method of any one of claims 1-92.

103. A system for quantifying ER pathway activity of a cancer in a subject, the system comprising a sequencer configured to generate a sequencing dataset from a sample; and a non- transitory computer readable storage medium of claim 101 and/or a computer system of claim 102.

104. The system of claim 103, wherein the sequencer is configured to generate a Whole Genome Sequencing (WGS) dataset from the sample.

105. The system of claim 103 or 104, further comprising a sample preparation device configured to prepare the sample for sequencing from a biological sample, optionally a liquid biopsy sample.

106. The system of claim 105, wherein the sample preparation device comprises reagents for quantifying one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and/or DNA methylation at one or more genomic loci in cell-free DNA (cfDNA) from the biological sample, optionally the liquid biopsy sample. Attorney Docket No: 2014191-0041

107. The system of claim 106, wherein the one or more genomic loci are selected from those listed Tables 1, 2, 3, 4, 5, 6, 9, or 10.

108. The system of any one of claims 103-107, wherein the device comprises reagents for quantifying H3K4me3 for: (a) at least 1, 5, 10, 20, 30, or 38 genomic loci listed in Table 1; (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 3; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 4; or (d) any combination of (a)-(c).

109. The system of any one of claims 103-108, wherein the kit comprises reagents for quantifying H3K27ac for: (a) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 2. (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 5; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 6; (d) at least 1, 5, 10, 20, 30, or 40 genomic loci listed in Table 9; (e) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 10; or (f) any combination of (a)-(e).

110. The system of any one of claims 103-109, wherein the device comprises reagents for quantifying H3K4me3, e.g., for: (a) at least 1, 5, 10, 20, 30, or 38 genomic loci listed in Table 1; (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 3; (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 4; or (d) any combination of (a)-(c).

111. The system of any one of claims 103-110, wherein the device comprises reagents for quantifying H3K27ac, e.g., for: (a) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 2. (b) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 5; Attorney Docket No: 2014191-0041 (c) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 6; (d) at least 1, 5, 10, 20, 30, or 40 genomic loci listed in Table 9; (e) at least 1, 5, 10, 20, 30, 40, or 50 genomic loci listed in Table 10; or (f) any combination of (a)-(e).

112. The system of any one of claims 103-111, wherein the reagents comprise one or more antibodies for use in ChIP-seq, optionally wherein the one or more antibodies specifically bind H3K4me3- or H3K27ac-modified histones.

113. The system of any one of claims 103-112, wherein the device comprises reagents for isolation of cell-free DNA (cfDNA) from the biological sample, optionally the liquid biopsy sample.

114. The system of any one of claims 103-113, wherein the device comprises reagents for library preparation for sequencing.

115. The system of any one of claims 103-114, wherein the sequencer comprises reagents for sequencing.