Aromatase inhibitors versus tamoxifen in early breast cancer

Patient-level meta-analysis of the randomised trials

Early Breast Cancer Trialists’ Collaborative Group

Research output: Contribution to journalArticle

389 Citations (Scopus)

Abstract

Background The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain. Methods We undertook meta-analyses of individual data on 31 920 postmenopausal women with oestrogen-receptorpositive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratifi ed by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen fi rst-event rate ratios (RRs). Findings In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors signifi cantly during years 0-1 (RR 0.64, 95% CI 0.52-0.78) and 2-4 (RR 0.80, 0.68-0.93), and non-signifi cantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12.1% vs 14.2%; RR 0.85, 0.75-0.96; 2p=0.009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors signifi cantly during years 0-1 (RR 0.74, 0.62-0.89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0.90, 0.81-0.99; 2p=0.045), though the breast cancer mortality reduction was not signifi cant (RR 0.89, 0.78-1.03; 2p=0.11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors signifi cantly during years 2-4 (RR 0.56, 0.46-0.67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8.7% vs 10.1%; 2p=0.015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments diff ered (RR 0.70, 0.64-0.77), but not signifi cantly thereafter (RR 0.93, 0.86-1.01; 2p=0.08). Breast cancer mortality was reduced both while treatments diff ered (RR 0.79, 0.67-0.92), and subsequently (RR 0.89, 0.81-0.99), and for all periods combined (RR 0.86, 0.80-0.94; 2p=0.0005). All-cause mortality was also reduced (RR 0.88, 0.82-0.94; 2p=0.0003). RRs diff ered little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0.4% vs 1.2%; RR 0.33, 0.21-0.51) but more bone fractures (5-year risk 8.2% vs 5.5%; RR 1.42, 1.28-1.57); non-breast-cancer mortality was similar. Interpretation Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments diff er, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment.

Original languageEnglish (US)
Pages (from-to)1341-1352
Number of pages12
JournalThe Lancet
Volume386
Issue number10001
DOIs
StatePublished - Oct 3 2015
Externally publishedYes

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Aromatase Inhibitors
Tamoxifen
Meta-Analysis
Breast Neoplasms
Mortality
Recurrence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Aromatase inhibitors versus tamoxifen in early breast cancer : Patient-level meta-analysis of the randomised trials. / Early Breast Cancer Trialists’ Collaborative Group.

In: The Lancet, Vol. 386, No. 10001, 03.10.2015, p. 1341-1352.

Research output: Contribution to journalArticle

Early Breast Cancer Trialists’ Collaborative Group. / Aromatase inhibitors versus tamoxifen in early breast cancer : Patient-level meta-analysis of the randomised trials. In: The Lancet. 2015 ; Vol. 386, No. 10001. pp. 1341-1352.
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title = "Aromatase inhibitors versus tamoxifen in early breast cancer: Patient-level meta-analysis of the randomised trials",
abstract = "Background The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain. Methods We undertook meta-analyses of individual data on 31 920 postmenopausal women with oestrogen-receptorpositive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratifi ed by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen fi rst-event rate ratios (RRs). Findings In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors signifi cantly during years 0-1 (RR 0.64, 95{\%} CI 0.52-0.78) and 2-4 (RR 0.80, 0.68-0.93), and non-signifi cantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12.1{\%} vs 14.2{\%}; RR 0.85, 0.75-0.96; 2p=0.009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors signifi cantly during years 0-1 (RR 0.74, 0.62-0.89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0.90, 0.81-0.99; 2p=0.045), though the breast cancer mortality reduction was not signifi cant (RR 0.89, 0.78-1.03; 2p=0.11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors signifi cantly during years 2-4 (RR 0.56, 0.46-0.67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8.7{\%} vs 10.1{\%}; 2p=0.015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments diff ered (RR 0.70, 0.64-0.77), but not signifi cantly thereafter (RR 0.93, 0.86-1.01; 2p=0.08). Breast cancer mortality was reduced both while treatments diff ered (RR 0.79, 0.67-0.92), and subsequently (RR 0.89, 0.81-0.99), and for all periods combined (RR 0.86, 0.80-0.94; 2p=0.0005). All-cause mortality was also reduced (RR 0.88, 0.82-0.94; 2p=0.0003). RRs diff ered little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0.4{\%} vs 1.2{\%}; RR 0.33, 0.21-0.51) but more bone fractures (5-year risk 8.2{\%} vs 5.5{\%}; RR 1.42, 1.28-1.57); non-breast-cancer mortality was similar. Interpretation Aromatase inhibitors reduce recurrence rates by about 30{\%} (proportionately) compared with tamoxifen while treatments diff er, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15{\%} compared with 5 years of tamoxifen, hence by about 40{\%} (proportionately) compared with no endocrine treatment.",
author = "{Early Breast Cancer Trialists’ Collaborative Group} and R. Bradley and J. Burrett and M. Clarke and C. Davies and F. Duane and V. Evans and L. Gettins and J. Godwin and R. Gray and H. Liu and P. McGale and E. MacKinnon and T. McHugh and S. James and P. Morris and H. Pan and R. Peto and S. Read and C. Taylor and Y. Wang and Z. Wang and M. Dowsett and Forbes, {J. F.} and J. Ingle and A. Coates and J. Cuzick and M. Gnant and T. Aihara and J. Bliss and F. Boccardo and Coombes, {R. C.} and P. Dubsky and M. Kaufmann and L. Kilburn and F. Perrone and D. Rea and B. Th{\"u}rlimann and {Van De Velde}, C. and M. Baum and A. Buzdar and I. Sestak and C. Markopoulos and C. Fesl and R. Jakesz and M. Colleoni and R. Gelber and M. Regan and {Von Minckwitz}, G. and C. Snowdon and Sparano, {Joseph A.}",
year = "2015",
month = "10",
day = "3",
doi = "10.1016/S0140-6736(15)61074-1",
language = "English (US)",
volume = "386",
pages = "1341--1352",
journal = "The Lancet",
issn = "0140-6736",
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TY - JOUR

T1 - Aromatase inhibitors versus tamoxifen in early breast cancer

T2 - Patient-level meta-analysis of the randomised trials

AU - Early Breast Cancer Trialists’ Collaborative Group

AU - Bradley, R.

AU - Burrett, J.

AU - Clarke, M.

AU - Davies, C.

AU - Duane, F.

AU - Evans, V.

AU - Gettins, L.

AU - Godwin, J.

AU - Gray, R.

AU - Liu, H.

AU - McGale, P.

AU - MacKinnon, E.

AU - McHugh, T.

AU - James, S.

AU - Morris, P.

AU - Pan, H.

AU - Peto, R.

AU - Read, S.

AU - Taylor, C.

AU - Wang, Y.

AU - Wang, Z.

AU - Dowsett, M.

AU - Forbes, J. F.

AU - Ingle, J.

AU - Coates, A.

AU - Cuzick, J.

AU - Gnant, M.

AU - Aihara, T.

AU - Bliss, J.

AU - Boccardo, F.

AU - Coombes, R. C.

AU - Dubsky, P.

AU - Kaufmann, M.

AU - Kilburn, L.

AU - Perrone, F.

AU - Rea, D.

AU - Thürlimann, B.

AU - Van De Velde, C.

AU - Baum, M.

AU - Buzdar, A.

AU - Sestak, I.

AU - Markopoulos, C.

AU - Fesl, C.

AU - Jakesz, R.

AU - Colleoni, M.

AU - Gelber, R.

AU - Regan, M.

AU - Von Minckwitz, G.

AU - Snowdon, C.

AU - Sparano, Joseph A.

PY - 2015/10/3

Y1 - 2015/10/3

N2 - Background The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain. Methods We undertook meta-analyses of individual data on 31 920 postmenopausal women with oestrogen-receptorpositive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratifi ed by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen fi rst-event rate ratios (RRs). Findings In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors signifi cantly during years 0-1 (RR 0.64, 95% CI 0.52-0.78) and 2-4 (RR 0.80, 0.68-0.93), and non-signifi cantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12.1% vs 14.2%; RR 0.85, 0.75-0.96; 2p=0.009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors signifi cantly during years 0-1 (RR 0.74, 0.62-0.89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0.90, 0.81-0.99; 2p=0.045), though the breast cancer mortality reduction was not signifi cant (RR 0.89, 0.78-1.03; 2p=0.11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors signifi cantly during years 2-4 (RR 0.56, 0.46-0.67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8.7% vs 10.1%; 2p=0.015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments diff ered (RR 0.70, 0.64-0.77), but not signifi cantly thereafter (RR 0.93, 0.86-1.01; 2p=0.08). Breast cancer mortality was reduced both while treatments diff ered (RR 0.79, 0.67-0.92), and subsequently (RR 0.89, 0.81-0.99), and for all periods combined (RR 0.86, 0.80-0.94; 2p=0.0005). All-cause mortality was also reduced (RR 0.88, 0.82-0.94; 2p=0.0003). RRs diff ered little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0.4% vs 1.2%; RR 0.33, 0.21-0.51) but more bone fractures (5-year risk 8.2% vs 5.5%; RR 1.42, 1.28-1.57); non-breast-cancer mortality was similar. Interpretation Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments diff er, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment.

AB - Background The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain. Methods We undertook meta-analyses of individual data on 31 920 postmenopausal women with oestrogen-receptorpositive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratifi ed by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen fi rst-event rate ratios (RRs). Findings In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors signifi cantly during years 0-1 (RR 0.64, 95% CI 0.52-0.78) and 2-4 (RR 0.80, 0.68-0.93), and non-signifi cantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12.1% vs 14.2%; RR 0.85, 0.75-0.96; 2p=0.009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors signifi cantly during years 0-1 (RR 0.74, 0.62-0.89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0.90, 0.81-0.99; 2p=0.045), though the breast cancer mortality reduction was not signifi cant (RR 0.89, 0.78-1.03; 2p=0.11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors signifi cantly during years 2-4 (RR 0.56, 0.46-0.67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8.7% vs 10.1%; 2p=0.015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments diff ered (RR 0.70, 0.64-0.77), but not signifi cantly thereafter (RR 0.93, 0.86-1.01; 2p=0.08). Breast cancer mortality was reduced both while treatments diff ered (RR 0.79, 0.67-0.92), and subsequently (RR 0.89, 0.81-0.99), and for all periods combined (RR 0.86, 0.80-0.94; 2p=0.0005). All-cause mortality was also reduced (RR 0.88, 0.82-0.94; 2p=0.0003). RRs diff ered little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0.4% vs 1.2%; RR 0.33, 0.21-0.51) but more bone fractures (5-year risk 8.2% vs 5.5%; RR 1.42, 1.28-1.57); non-breast-cancer mortality was similar. Interpretation Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments diff er, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment.

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