Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials - PubMed (original) (raw)
Meta-Analysis
. 2011 Aug 27;378(9793):771-84.
doi: 10.1016/S0140-6736(11)60993-8. Epub 2011 Jul 28.
C Davies, J Godwin, R Gray, M Clarke, D Cutter, S Darby, P McGale, H C Pan, C Taylor, Y C Wang, M Dowsett, J Ingle, R Peto
Collaborators
- PMID: 21802721
- PMCID: PMC3163848
- DOI: 10.1016/S0140-6736(11)60993-8
Meta-Analysis
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) et al. Lancet. 2011.
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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Figures
Figure 1
Relevance of measured ER and PR status to the effects of about 5 years of tamoxifen on the 10-year probability of recurrence Outcome by allocated treatment in trials of about 5 years of adjuvant tamoxifen. Event rate ratio (RR) is from summed log-rank statistics for all time periods. Gain (and its SE) is absolute difference between ends of graphs. ER=oestrogen receptor. PR=progesterone receptor. O–E=observed minus expected, with variance V.
Figure 2
Relevance of quantitative ER and PR measurement (fmol/mg cytosol protein) to the tamoxifen versus control recurrence rate ratio Outcome by allocated treatment in trials of about 5 years of adjuvant tamoxifen. Other ER poor includes ER-negative by immunohistochemistry and ER unspecified, but less than 10 fmol/mg. ER=oestrogen receptor. PR=progesterone receptor. O–E=observed minus expected.
Figure 3
Relevance of nodal status and of background chemotherapy to the effects of tamoxifen on the 10-year probability of recurrence, for ER-positive disease Outcome by allocated treatment in trials of about 5 years of adjuvant tamoxifen. Event rate ratio (RR) is from summed log-rank statistics for all time periods. Gain (and its SE) is absolute difference between ends of graphs. ER=oestrogen receptor. PR=progesterone receptor. O–E=observed minus expected, with variance V.
Figure 4
Subgroup analyses of the tamoxifen versus control recurrence rate ratio, for ER-positive disease Outcome by allocated treatment in trials of about 5 years of adjuvant tamoxifen. ER=oestrogen receptor. O–E=observed minus expected, with variance V.
Figure 5
Effects of about 5 years of tamoxifen on the 15-year probabilities of recurrence and of breast cancer mortality, for ER-positive disease Outcome by allocated treatment in trials of about 5 years of adjuvant tamoxifen. Event rate ratio (RR) is from summed log-rank statistics for all time periods. Gain (and its SE) is absolute difference between ends of graphs. ER=oestrogen receptor. O–E=observed minus expected, with variance V.
Figure 6
Relevance of intercurrent mortality in women younger than 45 years and 55–69 years of age to the absolute effects of tamoxifen on 15-year mortality, for ER-positive disease Outcome by allocated treatment in trials of about 5 years of adjuvant tamoxifen. Event rate ratio (RR) is from summed log-rank statistics for all time periods. Gain (and its SE) is absolute difference between ends of graphs. ER=oestrogen receptor. O–E=observed minus expected, with variance V.
Comment in
- With maturity comes confidence: EBCTCG tamoxifen update.
Chia SK, Wolff AC. Chia SK, et al. Lancet. 2011 Aug 27;378(9793):747-9. doi: 10.1016/S0140-6736(11)61128-8. Epub 2011 Jul 28. Lancet. 2011. PMID: 21802719 No abstract available. - ACP Journal Club. Meta-analysis: adjuvant tamoxifen reduces recurrence and death at 15 years in ER-positive early breast cancer.
Kiely B, Stockler M. Kiely B, et al. Ann Intern Med. 2012 Mar 20;156(6):JC3-4. doi: 10.7326/0003-4819-156-6-201203200-02004. Ann Intern Med. 2012. PMID: 22431690 No abstract available. - Telling details of breast-cancer recurrence.
Abderrahman B, Jordan VC. Abderrahman B, et al. Nature. 2018 Jan 11;553(7687):155. doi: 10.1038/d41586-018-00399-6. Nature. 2018. PMID: 29323320 No abstract available.
Similar articles
- Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Lancet. 2005 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0. Lancet. 2005. PMID: 15894097 - Tamoxifen for early breast cancer.
Early Breast Cancer Trialists' Collaborative Group. Early Breast Cancer Trialists' Collaborative Group. Cochrane Database Syst Rev. 2001;(1):CD000486. doi: 10.1002/14651858.CD000486. Cochrane Database Syst Rev. 2001. PMID: 11279694 Updated. Review. - WITHDRAWN: Tamoxifen for early breast cancer.
Clarke MJ. Clarke MJ. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD000486. doi: 10.1002/14651858.CD000486.pub2. Cochrane Database Syst Rev. 2008. PMID: 18843611 Free PMC article. Review. - Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Lancet Oncol. 2022 Mar;23(3):382-392. doi: 10.1016/S1470-2045(21)00758-0. Epub 2022 Feb 3. Lancet Oncol. 2022. PMID: 35123662 Free PMC article.
Cited by
- Tiaogan Bushen Xiaoji Formula Enhances the Sensitivity of Estrogen Receptor- Positive Breast Cancer to Tamoxifen by Inhibiting the TGF-β/SMAD Pathway.
Lu J, Li Z, Liu X, Xu B, Zhang W. Lu J, et al. Cancer Manag Res. 2024 Sep 9;16:1189-1204. doi: 10.2147/CMAR.S477399. eCollection 2024. Cancer Manag Res. 2024. PMID: 39282606 Free PMC article. - Abemaciclib Therapy Using the MonarchE Criteria Results in Large Numbers of Excess Axillary Node Clearances-Time to Pause and Reflect?
Ahari D, Wilkinson M, Ali N, Taxiarchi VP, Dave RV, Gandhi A. Ahari D, et al. Cancers (Basel). 2024 Sep 4;16(17):3072. doi: 10.3390/cancers16173072. Cancers (Basel). 2024. PMID: 39272930 Free PMC article. - Breast Cancer Risk Assessment Tool (BCRAT) and long-term breast cancer mortality in the Women's Health Initiative.
Nelson RA, Chlebowski RT, Pan K, Rohan TE, Mortimer J, Wactawski-Wende J, Lane DS, Kruper L. Nelson RA, et al. Breast Cancer Res Treat. 2024 Sep 10. doi: 10.1007/s10549-024-07470-z. Online ahead of print. Breast Cancer Res Treat. 2024. PMID: 39254768 - A narrative review: research progress of adjuvant intensive endocrine therapy for early breast cancer.
Ye H, Lin G, Wang X. Ye H, et al. Transl Breast Cancer Res. 2024 Jul 25;5:20. doi: 10.21037/tbcr-24-16. eCollection 2024. Transl Breast Cancer Res. 2024. PMID: 39184926 Free PMC article. Review. - Characterization of an Estrogen Receptor α-Selective 18 F-Estradiol PET Tracer.
Sluka P, Ackermann U, Rigopoulos A, Wardan H, Pezaro C, Burvenich IJG, Scott AM, Davis ID. Sluka P, et al. World J Nucl Med. 2024 Jun 18;23(3):153-160. doi: 10.1055/s-0044-1786518. eCollection 2024 Sep. World J Nucl Med. 2024. PMID: 39170834 Free PMC article.
References
- Early Breast Cancer Trialists' Collaborative Group (EBCTCG) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–1717. - PubMed
- Early Breast Cancer Trialists' Collaborative Group . Treatment of early breast cancer: worldwide evidence, 1985–1990. Oxford University Press; Oxford: 1990. http://www.ctsu.ox.ac.uk/reports/ebctcg-1990/index_html (accessed May 20, 2011).
- Dowsett M, Cuzick J, Ingle J. Meta-Analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors vs tamoxifen. J Clin Oncol. 2010;28:509–518. - PubMed
- Fisher B, Bryant J, Dignam JJ. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol. 2002;20:4141–4149. - PubMed
- Blamey RW, Chetty U, Bates T. Radiotherapy and/or Tamoxifen after conserving surgery for breast cancers of excellent prognosis: BASO II trial. Eur J Cancer Suppl. 2008;6:55. A17. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- 10588/CRUK_/Cancer Research UK/United Kingdom
- BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom
- MC_U137686850/MRC_/Medical Research Council/United Kingdom
- P30 CA008748/CA/NCI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials