Abstract

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.

Original languageEnglish
Pages (from-to)771-784
Number of pages14
JournalThe Lancet
Volume378
Issue number9793
DOIs
Publication statusPublished - Aug 27 2011

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Tamoxifen
Meta-Analysis
Hormones
Breast Neoplasms
Mortality
Recurrence
Drug Therapy
Numbers Needed To Treat
Uterine Neoplasms
Progesterone Receptors
Estrogen Receptors
Cytosol
Compliance
Biomedical Research
Neoplasms
Research

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen : Patient-level meta-analysis of randomised trials. / Early Breast Cancer Trialists' Collaborative Group (EBCTCG).

In: The Lancet, Vol. 378, No. 9793, 27.08.2011, p. 771-784.

Research output: Contribution to journalArticle

Early Breast Cancer Trialists' Collaborative Group (EBCTCG). / Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen : Patient-level meta-analysis of randomised trials. In: The Lancet. 2011 ; Vol. 378, No. 9793. pp. 771-784.
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abstract = "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.",
author = "{Early Breast Cancer Trialists' Collaborative Group (EBCTCG)} and O. Abe and R. Abe and K. Enomoto and K. Kikuchi and H. Koyama and H. Masuda and Y. Nomura and Y. Ohashi and K. Sakai and K. Sugimachi and M. Toi and T. Tominaga and J. Uchino and M. Yoshida and Haybittle, {J. L.} and Leonard, {C. F.} and G. Calais and P. Geraud and V. Collett and C. Davies and A. Delmestri and J. Sayer and Harvey, {V. J.} and Holdaway, {I. M.} and Kay, {R. G.} and D. Rea and N. Rotmensz and U. Veronesi and G. Viale and A. Costa and C. Tinterri and L. Gianni and Costa, {S. D.} and M. Sacco and M. Colleoni and A. Goldhirsch and P. Bruzzi and {Del Mastro}, L. and P. Pronzato and Sertoli, {M. R.} and {Di Mauro}, {M. G.} and D. Amadori and M. Lioce and A. Paradiso and {Del Mastro}, L. and S. Martino and A. Goldhirsch and F. Boccardo and A. Rubagotti and {De Laurentiis}, M.",
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TY - JOUR

T1 - Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen

T2 - Patient-level meta-analysis of randomised trials

AU - Early Breast Cancer Trialists' Collaborative Group (EBCTCG)

AU - Abe, O.

AU - Abe, R.

AU - Enomoto, K.

AU - Kikuchi, K.

AU - Koyama, H.

AU - Masuda, H.

AU - Nomura, Y.

AU - Ohashi, Y.

AU - Sakai, K.

AU - Sugimachi, K.

AU - Toi, M.

AU - Tominaga, T.

AU - Uchino, J.

AU - Yoshida, M.

AU - Haybittle, J. L.

AU - Leonard, C. F.

AU - Calais, G.

AU - Geraud, P.

AU - Collett, V.

AU - Davies, C.

AU - Delmestri, A.

AU - Sayer, J.

AU - Harvey, V. J.

AU - Holdaway, I. M.

AU - Kay, R. G.

AU - Rea, D.

AU - Rotmensz, N.

AU - Veronesi, U.

AU - Viale, G.

AU - Costa, A.

AU - Tinterri, C.

AU - Gianni, L.

AU - Costa, S. D.

AU - Sacco, M.

AU - Colleoni, M.

AU - Goldhirsch, A.

AU - Bruzzi, P.

AU - Del Mastro, L.

AU - Pronzato, P.

AU - Sertoli, M. R.

AU - Di Mauro, M. G.

AU - Amadori, D.

AU - Lioce, M.

AU - Paradiso, A.

AU - Del Mastro, L.

AU - Martino, S.

AU - Goldhirsch, A.

AU - Boccardo, F.

AU - Rubagotti, A.

AU - De Laurentiis, M.

PY - 2011/8/27

Y1 - 2011/8/27

N2 - 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.

AB - 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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