Between June 1970 and April 1975 the CRC (King's/Cambridge) Trial for early breast cancer randomi... more Between June 1970 and April 1975 the CRC (King's/Cambridge) Trial for early breast cancer randomized 2800 patients folowing mastectomy to immediate prophylactic radiotherapy (DXT group, n=1376) or control (WP group, n=1424). Although no difference in overall survival has been demonstrated, there is an increase in mortality in the irradiated patients from nonbreast cancer causes beyond 5 years. It is because of an increase in the number of deaths due to new nonbreast malignancies [RR=1.89 (1.18–3.05)] and to cardiac-related disease [RR=1.52 (1.01–2.29)]. This increased cardiac death rate may be related to the use of orthovoltage, which has greater scatter. There was a significant increase in risk for those with left-sided rather than right-sided tumors in this subgroup [χ2(int) = 5.08; p = 0.02]. Local relapse was significantly reduced in those patients randomized to radiotherapy [RR=0.44 (0.39–0.51)]. Median survival following local relapse was 1.35 years in the DXT group and 2.66 years in the WP group (logrank p<0.001). Patients with the first relapse in the supraclavicular nodes had a particularly poor prognosis (median survival: DXT 0.69 years; WP 1.37 years). Almost 50% of patients who have had a recurrence on the chest wall or in the axilla and subsequently died have had disease at the same site at death, regardless of whether they had radiotherapy immediately following surgery. However, the actual number of patients dying with persistent disease is halved by the use of prophylactic radiotherapy (DXT 66; WP 143). Classic pathologic features such as tumor size, tumor grade, and nodal involvement help define those patients at high risk of local failure who should be recommended for immediate radiotherapy. Entre Juin 1970 et Avril 1975, 2 800 femmes ont été randomisées dans l'essai CRC (King's/Cambridge) pour cancer du sein du début pour recevoir soit une radiothérapie prophylactique immédiate “DXT”, n=1376), soit rien (groupe de contrôle “WP”, n=1424) après mastectomie. Bien qu'aucune différence n'ait été démontrée dans la survie globale, on a constaté une augmentation de mortalité après 5 ans chez les patientes irradiées pour cancer (autre que le sein). Ceci est en rapport avec le nombre de décès secondaires aux cancers autres que du sein (RR=1.89 [1.8–3.05]) de même que ceux secondaires aux maladies cardiaques (RR=1.52 [1.01–2.29]). Cette mortalité cardiaque accrue est peut-être due à l'orthovoltage dont la répartition intéresse une plus large surface. Dans ce sous groupe, le risque de développer une tumeur est plus élevé à droite qu'à gauche (CHI2 (int)=5.08, p=0.02). La fréquence de récidive locale était diminuée de façon significative chez les patientes recevant la radíothérapie (RR=0.42 [0.36–0.48]). La survie médiane après récidive était de 1.35 ans chez les femmes dans le groupe DXT et de 2.66 ans chez les femmes dans le groupe WP (logrank p<0.001). Le pronostic des femmes dont la première récidive était dans les ganglions sus claviculaires était mauvais (survíe médiane: DXT=0.69 ans; WP=1.37 ans). Presque 50% des femmes ayant une récidive locale pariétale ou axillaire et décédées par la suite avaient un cancer à la même localisation au moment de leur décès qu'elles aient eu ou non une radiothérapie postopératoire immédiate. Le Entre junio de 1970 y abril de 1975, el ensayo clínico King's/Cambridge sobre cáncer mamario temprano incluyó 2800 pacientes randomizados luego de mastectomía y radioterapia profiláctica inmediata (grupo DXT, n=1376) o a control (grupo WP, n=1424). Aunque no se ha demostrado un incremento en la sobrevida global, sí se registra un incremento en la mortalidad por causas no de origen mamario en las pacientes irradiadas, más allá de los 5 años postirradiación. Esto se debe a un aumento en el número de muertes por neoplasias no mamarias (RR=1.89 [1.18–3.05]) así como a enfermedad relacionada con el corazón (RR=1.52 [1.01–2.29]). El incremento en las muertes de origen cardíaco puede ser debido al uso de ortovoltaje, el cual tiene una mayor dispersión. En este grupo se halló un incremento significativo en el riesgo para las pacientes con tumores en el lado izquierdo, en comparación con el derecho ([χ2(int) = 5.08; p = 0.02]. La tasa de recurrencia local se encontró significativamente menor en las pacientes randomizadas a radioterapia (RR=0.42 [0.36–0.48]). La sobrevida media luego de recurrencia local fue de 1.35 años en el grupo DXT y de 2.66 en el grupo WP (logrank p<0.001). Las pacientes que desarrollaron su primera recurrencia en los ganglios supraclaviculares exhibieron un pronóstico especialmente malo (sobrevida media: grupo DXT 0.69 años; grupo WP 1.37 años). Casi 50% de las pacientes que desarrollaron recurrencia en la pared del tórax o en la axila y que luego muríeron, presentaban enfermedad en el mismo sitio en el momento de la muerte, sin diferencia entre las que recibieron o no recibieron radioterapia inmediatamente después de la cirugía. Sin embargo, el número real de pacientes que murieron con enfermedad persistente se reduce a la mitad con el uso de la radioterapia profiláctica (grupo DXT 66; grupo WP 143). Las características clásicas, tales como tamaño del tumor, grado e invasión ganglionar, sirven para definir cuales pacientes son de alto riesgo de recurrencia local, en quienes se debe recomendar radioterapia inmediata.
Analysis from a multicenter trial of the management of operable breast cancer now in its fifteent... more Analysis from a multicenter trial of the management of operable breast cancer now in its fifteenth year has confirmed earlier published results that there are no significant differences in survival and distant recurrence between the two treatment groups (“watch policy” and radiotherapy). However, patients receiving prophylactic radiotherapy at the time of mastectomy continue to have a reduced risk of developing local recurrence as the first sign of treatment failure (p<0.001). This increased risk is related to various known prognostic indicators such as tumor size and histological grade. Detailed analysis of local recurrence data has shown protection for the radiotherapy patients against recurrence in the chest wall and axilla but not in the supraclavicular area. The question of uncontrolled local disease persisting to death has also been addressed. L'analyse récente d'un essai multicentrique de traitement du cancer du sein opérable conduit depuis 15 ans est venue confirmer les résultats publiés antérieurement: il n'y a pas de différence significative en ce qui concerne le taux de récidive tardive et le taux de survie globale que les malades soient ou non traités par irradiation, cependant les malades qui sont soumis à la radiothérapie prophylactique au moment de la mastectomie présentent moins de risques de récidive locale qui signifie l'échec du traitement (p<0,001). L'augmentation du taux de ce risque est fonction de divers facteurs de pronostic: volume de la tumeur et stade histologique du cancer. L'analyse plus détaillée des récidives après radiothérapie montre que celles-ci concernent la région supraclaviculaire mais n'intéressent pas la paroi thoracique et le creux axillaire. La question du caractère incurable de certaines lésions mammaires est également envisagée. El análisis de un ensayo interinstitucional de manejo del cáncer mamario operable, el cual se encuentra en el año 15 de ejecución, ha confirmado los resultados previamente publicados que indican que no existen diferencias significativas en la supervivencia ni en la recurrencia a largo plazo entre los dos grupos del estudio, el de la “política de observación” y el de radioterapia. Sin embargo, las pacientes que recibieron radioterapia profiláctica en el momento de la mastectomía continúan demostrando un menor riesgo de desarrollar recurrencia local como primera manifestación de la falla del tratamiento (p<0.001). El mayor riesgo de desarrollar recurrencia local aparece relacionado con varios indicadores de pronóstico, tales como el tamaño del tumor y su gradación histológica. El análisis detallado de los datos de recurrencia local ha demostrado protección de la recuerrencia local en la pared torácica y en la axila en las pacientes sometidas a radioterapia, pero no en el área supraclavicular. Persiste el interrogante sobre la enfermedad local no controlable que persiste hasta la muerte, fenómeno que es causa de angustia para la paciente. Tal situación fué de ocurrencia mayor en le grupo de “política de observación” que en el de radioterapia.
ABSTRACT The objective of this study was to determine the impact of offering women choice in deci... more ABSTRACT The objective of this study was to determine the impact of offering women choice in decision-making about surgery in early breast cancer. We examined how women felt about choosing, which choices they made and the effect that choosing had on psychiatric morbidity over 3 years.269 women with stage I or II breast cancer were treated by three groups of surgeons, who either favoured mastectomy or breast conserving surgery or who offered patients choice whenever possible.Results revealed that a significant minority of women experienced unremitting psychiatric morbidity, irrespective of surgeon group or actual surgery performed. At 3 years, 19% of women were clinically anxious and 15% were depressed. With 3-year follow-up, the relative risk (95% CI) for psychiatric morbidity was less in women treated by ‘choice’ surgeons, compared to women treated by surgeons favouring mastectomy (p &lt; 0.05). 62 women were eligible to choose their surgery, and of these 8 (13%) were unable to make a decision. Difficulty was experienced by (37%) of women. Nevertheless, (42%) felt pleased that they had been allowed to choose, although others had some reservations about the process. Only 5 women expressed doubts about their original decision. There was no evidence that choice in itself prevents psychiatric morbidity in women treated for breast cancer.
International Journal of Technology Assessment in Health Care, 1989
Physicians through the ages have practiced their trade with more or less regard to the effects of... more Physicians through the ages have practiced their trade with more or less regard to the effects of their treatment on their patients&#39; sense of well-being, if not as much as on the disease itself. Until recently, however, little attempt has been made to measure the effect of disease upon quality of life and how this quality is or is not improved by the treatment. Several means have now evolved and in areas of medicine where the treatment may profoundly affect the patient&#39;s sense of well-being, effort is being made to gauge these consequences.
The molecular mechanism of action of anti-oestrogens such as tamoxifen appears to be a complex mi... more The molecular mechanism of action of anti-oestrogens such as tamoxifen appears to be a complex mixture of antagonism of the mitogenic action of oestradiol at the level of the oestrogen receptor, plus a range of other activities from enzyme inhibition to growth factor modulation. This article will concentrate on two specific areas: 1) the inhibition of protein kinase C and calmodulin-dependent cAMP phosphodiesterase; and 2) the regulation by tamoxifen of peptide regulators of breast cancer epithelial cell growth such as insulin-like growth factor I (IGF I) and transforming growth factor beta (TGF-β). The elucidation of these mechanisms is potentially important in the treatment and chemoprevention of breast cancer — the quantitative contribution of each individual mechanism of the overall antineoplastic action of anti-oestrogens is central to developing new and possibly more effective anti-oestrogens and optimizing strategies for their use.
Between June 1970 and April 1975 the CRC (King's/Cambridge) Trial for early breast cancer randomi... more Between June 1970 and April 1975 the CRC (King's/Cambridge) Trial for early breast cancer randomized 2800 patients folowing mastectomy to immediate prophylactic radiotherapy (DXT group, n=1376) or control (WP group, n=1424). Although no difference in overall survival has been demonstrated, there is an increase in mortality in the irradiated patients from nonbreast cancer causes beyond 5 years. It is because of an increase in the number of deaths due to new nonbreast malignancies [RR=1.89 (1.18–3.05)] and to cardiac-related disease [RR=1.52 (1.01–2.29)]. This increased cardiac death rate may be related to the use of orthovoltage, which has greater scatter. There was a significant increase in risk for those with left-sided rather than right-sided tumors in this subgroup [χ2(int) = 5.08; p = 0.02]. Local relapse was significantly reduced in those patients randomized to radiotherapy [RR=0.44 (0.39–0.51)]. Median survival following local relapse was 1.35 years in the DXT group and 2.66 years in the WP group (logrank p<0.001). Patients with the first relapse in the supraclavicular nodes had a particularly poor prognosis (median survival: DXT 0.69 years; WP 1.37 years). Almost 50% of patients who have had a recurrence on the chest wall or in the axilla and subsequently died have had disease at the same site at death, regardless of whether they had radiotherapy immediately following surgery. However, the actual number of patients dying with persistent disease is halved by the use of prophylactic radiotherapy (DXT 66; WP 143). Classic pathologic features such as tumor size, tumor grade, and nodal involvement help define those patients at high risk of local failure who should be recommended for immediate radiotherapy. Entre Juin 1970 et Avril 1975, 2 800 femmes ont été randomisées dans l'essai CRC (King's/Cambridge) pour cancer du sein du début pour recevoir soit une radiothérapie prophylactique immédiate “DXT”, n=1376), soit rien (groupe de contrôle “WP”, n=1424) après mastectomie. Bien qu'aucune différence n'ait été démontrée dans la survie globale, on a constaté une augmentation de mortalité après 5 ans chez les patientes irradiées pour cancer (autre que le sein). Ceci est en rapport avec le nombre de décès secondaires aux cancers autres que du sein (RR=1.89 [1.8–3.05]) de même que ceux secondaires aux maladies cardiaques (RR=1.52 [1.01–2.29]). Cette mortalité cardiaque accrue est peut-être due à l'orthovoltage dont la répartition intéresse une plus large surface. Dans ce sous groupe, le risque de développer une tumeur est plus élevé à droite qu'à gauche (CHI2 (int)=5.08, p=0.02). La fréquence de récidive locale était diminuée de façon significative chez les patientes recevant la radíothérapie (RR=0.42 [0.36–0.48]). La survie médiane après récidive était de 1.35 ans chez les femmes dans le groupe DXT et de 2.66 ans chez les femmes dans le groupe WP (logrank p<0.001). Le pronostic des femmes dont la première récidive était dans les ganglions sus claviculaires était mauvais (survíe médiane: DXT=0.69 ans; WP=1.37 ans). Presque 50% des femmes ayant une récidive locale pariétale ou axillaire et décédées par la suite avaient un cancer à la même localisation au moment de leur décès qu'elles aient eu ou non une radiothérapie postopératoire immédiate. Le Entre junio de 1970 y abril de 1975, el ensayo clínico King's/Cambridge sobre cáncer mamario temprano incluyó 2800 pacientes randomizados luego de mastectomía y radioterapia profiláctica inmediata (grupo DXT, n=1376) o a control (grupo WP, n=1424). Aunque no se ha demostrado un incremento en la sobrevida global, sí se registra un incremento en la mortalidad por causas no de origen mamario en las pacientes irradiadas, más allá de los 5 años postirradiación. Esto se debe a un aumento en el número de muertes por neoplasias no mamarias (RR=1.89 [1.18–3.05]) así como a enfermedad relacionada con el corazón (RR=1.52 [1.01–2.29]). El incremento en las muertes de origen cardíaco puede ser debido al uso de ortovoltaje, el cual tiene una mayor dispersión. En este grupo se halló un incremento significativo en el riesgo para las pacientes con tumores en el lado izquierdo, en comparación con el derecho ([χ2(int) = 5.08; p = 0.02]. La tasa de recurrencia local se encontró significativamente menor en las pacientes randomizadas a radioterapia (RR=0.42 [0.36–0.48]). La sobrevida media luego de recurrencia local fue de 1.35 años en el grupo DXT y de 2.66 en el grupo WP (logrank p<0.001). Las pacientes que desarrollaron su primera recurrencia en los ganglios supraclaviculares exhibieron un pronóstico especialmente malo (sobrevida media: grupo DXT 0.69 años; grupo WP 1.37 años). Casi 50% de las pacientes que desarrollaron recurrencia en la pared del tórax o en la axila y que luego muríeron, presentaban enfermedad en el mismo sitio en el momento de la muerte, sin diferencia entre las que recibieron o no recibieron radioterapia inmediatamente después de la cirugía. Sin embargo, el número real de pacientes que murieron con enfermedad persistente se reduce a la mitad con el uso de la radioterapia profiláctica (grupo DXT 66; grupo WP 143). Las características clásicas, tales como tamaño del tumor, grado e invasión ganglionar, sirven para definir cuales pacientes son de alto riesgo de recurrencia local, en quienes se debe recomendar radioterapia inmediata.
Analysis from a multicenter trial of the management of operable breast cancer now in its fifteent... more Analysis from a multicenter trial of the management of operable breast cancer now in its fifteenth year has confirmed earlier published results that there are no significant differences in survival and distant recurrence between the two treatment groups (“watch policy” and radiotherapy). However, patients receiving prophylactic radiotherapy at the time of mastectomy continue to have a reduced risk of developing local recurrence as the first sign of treatment failure (p<0.001). This increased risk is related to various known prognostic indicators such as tumor size and histological grade. Detailed analysis of local recurrence data has shown protection for the radiotherapy patients against recurrence in the chest wall and axilla but not in the supraclavicular area. The question of uncontrolled local disease persisting to death has also been addressed. L'analyse récente d'un essai multicentrique de traitement du cancer du sein opérable conduit depuis 15 ans est venue confirmer les résultats publiés antérieurement: il n'y a pas de différence significative en ce qui concerne le taux de récidive tardive et le taux de survie globale que les malades soient ou non traités par irradiation, cependant les malades qui sont soumis à la radiothérapie prophylactique au moment de la mastectomie présentent moins de risques de récidive locale qui signifie l'échec du traitement (p<0,001). L'augmentation du taux de ce risque est fonction de divers facteurs de pronostic: volume de la tumeur et stade histologique du cancer. L'analyse plus détaillée des récidives après radiothérapie montre que celles-ci concernent la région supraclaviculaire mais n'intéressent pas la paroi thoracique et le creux axillaire. La question du caractère incurable de certaines lésions mammaires est également envisagée. El análisis de un ensayo interinstitucional de manejo del cáncer mamario operable, el cual se encuentra en el año 15 de ejecución, ha confirmado los resultados previamente publicados que indican que no existen diferencias significativas en la supervivencia ni en la recurrencia a largo plazo entre los dos grupos del estudio, el de la “política de observación” y el de radioterapia. Sin embargo, las pacientes que recibieron radioterapia profiláctica en el momento de la mastectomía continúan demostrando un menor riesgo de desarrollar recurrencia local como primera manifestación de la falla del tratamiento (p<0.001). El mayor riesgo de desarrollar recurrencia local aparece relacionado con varios indicadores de pronóstico, tales como el tamaño del tumor y su gradación histológica. El análisis detallado de los datos de recurrencia local ha demostrado protección de la recuerrencia local en la pared torácica y en la axila en las pacientes sometidas a radioterapia, pero no en el área supraclavicular. Persiste el interrogante sobre la enfermedad local no controlable que persiste hasta la muerte, fenómeno que es causa de angustia para la paciente. Tal situación fué de ocurrencia mayor en le grupo de “política de observación” que en el de radioterapia.
ABSTRACT The objective of this study was to determine the impact of offering women choice in deci... more ABSTRACT The objective of this study was to determine the impact of offering women choice in decision-making about surgery in early breast cancer. We examined how women felt about choosing, which choices they made and the effect that choosing had on psychiatric morbidity over 3 years.269 women with stage I or II breast cancer were treated by three groups of surgeons, who either favoured mastectomy or breast conserving surgery or who offered patients choice whenever possible.Results revealed that a significant minority of women experienced unremitting psychiatric morbidity, irrespective of surgeon group or actual surgery performed. At 3 years, 19% of women were clinically anxious and 15% were depressed. With 3-year follow-up, the relative risk (95% CI) for psychiatric morbidity was less in women treated by ‘choice’ surgeons, compared to women treated by surgeons favouring mastectomy (p &lt; 0.05). 62 women were eligible to choose their surgery, and of these 8 (13%) were unable to make a decision. Difficulty was experienced by (37%) of women. Nevertheless, (42%) felt pleased that they had been allowed to choose, although others had some reservations about the process. Only 5 women expressed doubts about their original decision. There was no evidence that choice in itself prevents psychiatric morbidity in women treated for breast cancer.
International Journal of Technology Assessment in Health Care, 1989
Physicians through the ages have practiced their trade with more or less regard to the effects of... more Physicians through the ages have practiced their trade with more or less regard to the effects of their treatment on their patients&#39; sense of well-being, if not as much as on the disease itself. Until recently, however, little attempt has been made to measure the effect of disease upon quality of life and how this quality is or is not improved by the treatment. Several means have now evolved and in areas of medicine where the treatment may profoundly affect the patient&#39;s sense of well-being, effort is being made to gauge these consequences.
The molecular mechanism of action of anti-oestrogens such as tamoxifen appears to be a complex mi... more The molecular mechanism of action of anti-oestrogens such as tamoxifen appears to be a complex mixture of antagonism of the mitogenic action of oestradiol at the level of the oestrogen receptor, plus a range of other activities from enzyme inhibition to growth factor modulation. This article will concentrate on two specific areas: 1) the inhibition of protein kinase C and calmodulin-dependent cAMP phosphodiesterase; and 2) the regulation by tamoxifen of peptide regulators of breast cancer epithelial cell growth such as insulin-like growth factor I (IGF I) and transforming growth factor beta (TGF-β). The elucidation of these mechanisms is potentially important in the treatment and chemoprevention of breast cancer — the quantitative contribution of each individual mechanism of the overall antineoplastic action of anti-oestrogens is central to developing new and possibly more effective anti-oestrogens and optimizing strategies for their use.
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