Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen : patient-level meta-analysis of randomised trials
(2011) In The Lancet 378(9793). p.771-784- 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... (More)
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.
(Less)
- contributor
- Malmström, Per LU
- author collaboration
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Antineoplastic Agents, Hormonal/adverse effects, Breast Neoplasms/drug therapy, Chemotherapy, Adjuvant, Female, Humans, Neoplasm Recurrence, Local/prevention & control, Neoplasms, Second Primary/chemically induced, Randomized Controlled Trials as Topic, Receptors, Estrogen/metabolism, Receptors, Progesterone/metabolism, Selective Estrogen Receptor Modulators/adverse effects, Tamoxifen/adverse effects
- in
- The Lancet
- volume
- 378
- issue
- 9793
- pages
- 771 - 784
- publisher
- Elsevier
- external identifiers
-
- pmid:21802721
- scopus:85181122894
- ISSN
- 0140-6736
- DOI
- 10.1016/S0140-6736(11)60993-8
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2011 Elsevier Ltd. All rights reserved.
- id
- ec2d570a-4465-4e51-978e-10a59583d3fd
- date added to LUP
- 2024-02-06 11:56:35
- date last changed
- 2024-06-19 18:20:26
@article{ec2d570a-4465-4e51-978e-10a59583d3fd,
abstract = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>FUNDING: Cancer Research UK, British Heart Foundation, and Medical Research Council.</p>}},
issn = {{0140-6736}},
keywords = {{Antineoplastic Agents, Hormonal/adverse effects; Breast Neoplasms/drug therapy; Chemotherapy, Adjuvant; Female; Humans; Neoplasm Recurrence, Local/prevention & control; Neoplasms, Second Primary/chemically induced; Randomized Controlled Trials as Topic; Receptors, Estrogen/metabolism; Receptors, Progesterone/metabolism; Selective Estrogen Receptor Modulators/adverse effects; Tamoxifen/adverse effects}},
language = {{eng}},
number = {{9793}},
pages = {{771--784}},
publisher = {{Elsevier}},
series = {{The Lancet}},
title = {{Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen : patient-level meta-analysis of randomised trials}},
url = {{http://dx.doi.org/10.1016/S0140-6736(11)60993-8}},
doi = {{10.1016/S0140-6736(11)60993-8}},
volume = {{378}},
year = {{2011}},
}