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

TitleRelevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials
Authors
Issue Date2011
PublisherThe Lancet Publishing Group. The Journal's web site is located at http://www.elsevier.com/locate/lancet
Citation
The Lancet, 2011, v. 378 n. 9793, p. 771-784 How to Cite?
AbstractBACKGROUND: 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.
Persistent Identifierhttp://hdl.handle.net/10722/163926
ISSN
2015 Impact Factor: 44.002
2015 SCImago Journal Rankings: 14.638
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKwong, DLWen_US
dc.contributor.authorDavies, Cen_US
dc.contributor.authorGodwin, Jen_US
dc.contributor.authorGray, Ren_US
dc.contributor.authorClarke, Men_US
dc.contributor.authorCutter, Den_US
dc.contributor.authorDarby, Sen_US
dc.contributor.authorMcGale, Pen_US
dc.contributor.authorPan, HCen_US
dc.contributor.authorTaylor, Cen_US
dc.contributor.authorWang, YCen_US
dc.contributor.authorDowsett, Men_US
dc.contributor.authorIngle, Jen_US
dc.contributor.authorPeto, Ren_US
dc.date.accessioned2012-09-20T07:53:16Z-
dc.date.available2012-09-20T07:53:16Z-
dc.date.issued2011en_US
dc.identifier.citationThe Lancet, 2011, v. 378 n. 9793, p. 771-784en_US
dc.identifier.issn0140-6736-
dc.identifier.urihttp://hdl.handle.net/10722/163926-
dc.description.abstractBACKGROUND: 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.-
dc.languageengen_US
dc.publisherThe Lancet Publishing Group. The Journal's web site is located at http://www.elsevier.com/locate/lancet-
dc.relation.ispartofThe Lanceten_US
dc.subject.meshAntineoplastic Agents, Hormonal - adverse effects - therapeutic use-
dc.subject.meshBreast Neoplasms - drug therapy - metabolism - mortality - pathology-
dc.subject.meshReceptors, Estrogen - metabolism-
dc.subject.meshReceptors, Progesterone - metabolism-
dc.subject.meshTamoxifen - adverse effects - therapeutic use-
dc.titleRelevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trialsen_US
dc.typeArticleen_US
dc.identifier.emailKwong, DLW: dlwkwong@hku.hken_US
dc.identifier.authorityKwong, DLW=rp00414en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/S0140-6736(11)60993-8-
dc.identifier.pmid21802721-
dc.identifier.pmcidPMC3163848-
dc.identifier.scopuseid_2-s2.0-80052262856-
dc.identifier.hkuros210569en_US
dc.identifier.volume378en_US
dc.identifier.issue9793en_US
dc.identifier.spage771en_US
dc.identifier.epage784en_US
dc.identifier.isiWOS:000294585300033-
dc.publisher.placeUnited Kingdom-
dc.identifier.citeulike9784457-

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