Abstract
Adjuvant hormonal therapy significantly improves long-term survival of breast cancer patients with hormone receptor-positive disease. Despite the proven clinical efficacy of tamoxifen and aromatase inhibitors, many breast cancer survivors either fail to take the correct dosage at the prescribed frequency (adherence) or discontinue therapy (persistence). This systematic review aims to: (1) determine the prevalence of adherence and persistence to adjuvant hormonal therapy among breast cancer survivors in clinical practice, and (2) identify correlates of adherence and persistence. We searched Medline, PubMed, PsycINFO, and CINAHL for studies that measured rates and/or correlates of adherence and/or persistence to adjuvant hormonal therapy. Studies were reviewed in a multi-step process: (1) the lead author screened titles and abstracts of all potentially eligible studies; (2) each coauthor reviewed a random 5 % sample of abstracts; and (3) two sets of coauthors each reviewed half of all “maybe” abstracts. Any disagreements were discussed until consensus was reached. Twenty-nine studies met inclusion criteria. Prevalence of adherence ranged from 41 to 72 % and discontinuation (i.e., nonpersistence) ranged from 31 to 73 %, measured at the end of 5 years of treatment. Extremes of age (older or younger), increasing out-of-pocket costs, follow-up care with a general practitioner (vs. oncologist), higher CYP2D6 activity, switching from one form of therapy to another, and treatment side effects were negatively associated with adherence and/or persistence. Taking more medications at baseline, referral to an oncologist, and earlier year at diagnosis were positively associated with adherence and/or persistence. Adherence and persistence to adjuvant hormonal therapy among breast cancer survivors is suboptimal. Many of the correlates of adherence and persistence studied to date are not modifiable. Our review reveals a critical need for further research on modifiable factors associated with adherence to adjuvant hormonal therapy, and the development of behavioral interventions to improve adherence in this population.
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Acknowledgments
This study was partially supported by the National Cancer Institute at the National Institutes of Health (K07CA140159 to Dr. Carpentier and R01CA112223 to Dr. Vernon) and the Susan G. Komen Foundation (KG111378 to Ms. Bluethmann). The authors would like to thank Helena VonVille for her assistance in developing the search strategy.
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Appendix
Appendix
Search strategy for Ovid Medline
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1.
exp patient compliance/or treatment refusal/
-
2.
(nonadherence or non-adherence or adherence or continuance or persist* or complian* or discontinu*).ti,ab.
-
3.
1 or 2
-
4.
exp Tamoxifen/
-
5.
tamoxifen.ti,ab.
-
6.
Estrogen Antagonists/
-
7.
exp Aromatase Inhibitors/
-
8.
aromatase inhibitor*.ti,ab.
-
9.
Antineoplastic Agents, Hormonal/
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10.
(adjuvant endocrine therap* or adjuvant hormonal therap*).ti,ab.
-
11.
or/4-10
-
12.
breast neoplasms/or (breast adj3 (cancer* or neoplasm*)).ti,ab.
-
13.
3 and 11 and 12
-
14.
limit 13 to yr = “1998 - 2012”
-
15.
limit 14 to english language
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16.
(15 not animals/) or (15 and humans/)
Search strategy for PubMed
-
1.
Search patient compliance[mesh] OR treatment refusal[mesh:noexp]
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2.
Search nonadherence[tiab] OR non-adherence[tiab] OR adherence[tiab] OR continuance[tiab] OR persist*[tiab] OR complian*[tiab] OR discontinu*[tiab]
-
3.
Search #1 OR #2
-
4.
Search Tamoxifen[mesh]
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5.
Search tamoxifen[tiab]
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6.
Search Estrogen Antagonists[mesh:noexp]
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7.
Search Aromatase Inhibitors[mesh]
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8.
Search aromatase inhibitor*[tiab]
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9.
Search Antineoplastic Agents, Hormonal[mesh:noexp]
-
10.
Search adjuvant endocrine therap*[tiab] OR adjuvant hormonal therap*[tiab]
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11.
Search #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10
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12.
Search breast neoplasms[mesh:noexp] OR (breast[tiab] AND (cancer*[tiab] OR neoplasm*[tiab]))
-
13.
Search #3 AND #11 AND #12
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14.
Search (#13 NOT animals[mesh:noexp]) OR (#13 AND humans[mesh])
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15.
Search #14 Limits: English, Publication Date from 1998 to 2012
Search strategy for PsycINFO
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1.
exp compliance/or disease management/or treatment barriers/or treatment dropouts/or treatment duration/or treatment refusal/
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2.
(nonadherence or non-adherence or adherence or continuance or persist* or complian* or discontinu*).ti,ab,id.
-
3.
1 or 2
-
4.
antiestrogens/
-
5.
(tamoxifen or aromatase inhibitor* or adjuvant endocrine therap* or adjuvant hormonal therap*).ti, ab,id.
-
6.
4 or 5
-
7.
exp Breast Neoplasms/
-
8.
(breast adj3 (cancer* or neoplasm*)).ti,ab,id.
-
9.
7 or 8
-
10.
3 and 6 and 9
Search strategy for CINAHL
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S1.
(MH “Breast Neoplasms”) or (breast cancer* or breast neoplasm*)
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S2.
(MH “Estrogen Antagonists+”) or (MH “Antineoplastic Agents, Hormonal+”) or TI (tamoxifen or estrogen antagonist* or adjuvant endocrine therap* OR adjuvant hormonal therap* OR aromatase inhibitor*) or AB (tamoxifen or estrogen antagonist* or adjuvant endocrine therap* OR adjuvant hormonal therap* OR aromatase inhibitor*)
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S3.
((MH “Patient Compliance+”) OR (MH “Treatment Refusal”)) or TI ((nonadherence or non-adherence or adherence or continuance or persist* or complian* or discontinu*)) or AB ((nonadherence or non-adherence or adherence or continuance or persist* or complian* or discontinu*))
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S4.
S1 and S2 and S3
-
S5.
S1 and S2 and S3 Limiters - Published Date from: 19980101-20121231; English Language
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Murphy, C.C., Bartholomew, L.K., Carpentier, M.Y. et al. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 134, 459–478 (2012). https://doi.org/10.1007/s10549-012-2114-5
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DOI: https://doi.org/10.1007/s10549-012-2114-5