Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials : The Lancet

open here please ►Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials : The Lancet: "The Lancet, Early Online Publication, 29 July 2011
doi:10.1016/S0140-6736(11)60993-8Cite or Link Using DOI
Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials

Original Text
Early Breast Cancer Trialists' Collaborative Group (EBCTCG) ‡Corresponding AuthorEmail Address


Summary
Background
As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen.

Methods
We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21 457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment.

Findings
In oestrogen receptor (ER)-positive disease (n=10 645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0—4 and RR 0·68 [0·06] during years 5—9 [both 2p<0·00001]; but RR 0·97 [0·10] during years 10—14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10—19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0·71 [0·05] during years 0—4, 0·66 [0·05] during years 5—9, and 0·68 [0·08] during years 10—14; p<0·0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality.

Interpretation
5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the only recorded factor importantly predictive of the proportional reductions. Hence, the absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamoxifen.

Funding
Cancer Research UK, British Heart Foundation, and Medical Research Council.

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Early Breast Cancer Trialists' Collaborative Group (EBCTCG) — CTSU: "Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
EBCTCG Collaborators: login here

* EBCTCG Rationale and Timetable (Updated 07 July 2010)
* EBCTCG 6 (2010-2012) Main Variable List (Draft of June 2010)
* EBCTCG 6 (2010-2012) DCIS Variable List (Draft of June 2010)

400,000 women in 400 randomised trials

Every five years, CTSU brings together updated data on each woman randomised into all trials of the treatment of operable breast cancer. The EBCTCG process was initiated in 1983 and the first cycle collected data for hormonal and cytotoxic therapy in 1985 [6a, 6b]. The collaboration was extended in the 1990s to all aspects of early breast cancer management [7a - 7f] and its results informed the year 2000 NIH consensus development conference on the treatment of early breast cancer [8]. The 2005 report on chemotherapy and endocrine therapy [9a] shows the substantial effects on 15-year survival of the chemotherapy regimens (such as about 6 months of FAC or FEC in women aged <70) and hormonal regimens (such as at least 5 years of tamoxifen in women with ER+ disease) that were being tested in the 1980s. The 2005 report on surgery and radiotherapy [9b] shows that treatments that substantially improve local control have little effect on breast cancer mortality during the first few years, but definite effects by 15 years.

Results from the fifth cycle are emerging (ER-poor [10a], DCIS [10b], aromatase inhibitors [10c], chemotherapy [in preparation], endocrine therapy [in preparation], radiotherapy [in preparation]) while the sixth (2010-2012) cycle of data collection is in progress.

* Results from EBCTCG Fourth Cycle (2000 data) and Fifth Cycle (2005-2006 data)
* Original methods for EBCTCG meta-analyses
* Brief history of EBCTCG prior to 2005

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Actualidad Ultimas noticias - JANOes - Los canceres de mama tratados con tamoxifeno presentan un menor riesgo de reproduccion - JANO.es - ELSEVIER: "GINECOLOGÍA
Los cánceres de mama tratados con tamoxifeno presentan un menor riesgo de reproducción

JANO.es · 01 Agosto 2011 00:32


Este fármaco, usado durante más de 30 años para tratar los tumores con receptores de estrógeno positivos, ha sido reemplazado en mujeres posmenopáusicas por inhibidores de la aromatasa.

Las pacientes de cáncer de mama tratadas con tamoxifeno durante cinco años presentan casi un 40% menos de probabilidades de que el cáncer se reproduzca. Esta protección dura más de una década tras dejar de tomar el fármaco, según acaba de documentar un estudio publicado en Lancet.

Los investigadores analizaron los resultados de un ensayo en el que participaron 21.000 mujeres de una docena de países, y de las que el 50% tomaba tamoxifeno.15 años después del diagnóstico, y 10 después de dejar de tomar el fármaco, las mujeres que tomaron tamoxifeno presentaban un riesgo de muerte un tercio menor al de las que no lo tomaron.

'Es un fármaco importante', aseguró la autora del estudio, la Dra. Christina Davies, investigadora principal del Early Breast Cancer Trialists Collaborative Group. 'Probablemente', añade, 'sea el medicamento oncológico que más vidas ha salvado'.

De las 10.645 mujeres que tomaron tamoxifeno, alrededor del 26% tuvo un relapso a los 10 años, frente al 40% de las que no lo tomaron. A los 15 años, al 33% de las mujeres que tomaron el fármaco se les reprodujo el cáncer, frente al 46% de las que no lo tomaron.

Las estadísticas fueron similares en cuanto a las tasas de mortalidad. Tras una década, alrededor del 25% de las mujeres que no tomaron el fármaco había muerto, frente al 18% de las que sí lo tomaron. A los 15 años, el 33% de las que no habían tomado el medicamento habían muerto, en comparación con el 24% de las que tomaron tamoxifeno. 'No solo se beneficiaron mientras tomaban el fármaco, sino durante muchos años más', aseguró la Dra. Davies.

Riesgo 'casi inexistente'

El tamoxifeno se ha usado durante más de 30 años para tratar el tipo más común de cáncer de mama, los tumores con receptores de estrógeno positivos. Actualmente, las mujeres posmenopáusicas reciben una clase más reciente de fármacos, los inhibidores de la aromatasa, que bloquean el estrógeno liberado en la grasa corporal. Los inhibidores de la aromatasa se usan con más facilidad en mujeres que ya no tienen ovarios que produzcan estrógeno, explicó la Dra, Davies.

Un motivo del cambio a los inhibidores de la aromatasa es que investigaciones anteriores, además del estudio actual, hallaron que el tamoxifeno aumenta el riesgo de cáncer endometrial y de coágulos potencialmente mortales en los pulmones. Con todo, un análisis halló que el riesgo añadido del tamoxifeno para las mujeres mayores era pequeño, y en las más jóvenes 'casi inexistente', explicó la Dra. Davies.


Lancet 2011;doi:10.1016/S0140-6736(11)60993-8
Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials : The Lancet: "- Enviado mediante la barra Google"

Early Breast Cancer Trialists Collaborative Group
Early Breast Cancer Trialists' Collaborative Group (EBCTCG) — CTSU: "- Enviado mediante la barra Google"
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