Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen

Mitch Dowsett, Jack Cuzick, Jim Ingle, Alan Coates, John Forbes, Judith Bliss, Marc Buyse, Michael Baum, Aman Buzdar, Marco Colleoni, Charles Coombes, Claire Snowdon, Michael Gnant, Raimund Jakesz, Manfred Kaufmann, Francesco Boccardo, Jon Godwin, Christina Davies, Richard Peto

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Abstract

Purpose: To conduct meta-analyses of randomized trials of aromatase inhibitors (AIs) compared with tamoxifen either as initial monotherapy (cohort 1) or after 2 to 3 years of tamoxifen (cohort 2). Materials and Methods: Data submitted to the Early Breast Cancer Trialists' Collaborative Group were used in separate meta-analyses of two cohorts. Primary analyses involve postmenopausal women with tumors reported to be estrogen receptor positive. Log-rank P values are two-sided. Results: Cohort 1 comprised 9,856 patients with a mean of 5.8 years of follow-up. At 5 years, AI therapy was associated with an absolute 2.9% (SE = 0.7%) decrease in recurrence (9.6% for AI v 12.6% for tamoxifen; 2P <.00001) and a nonsignificant absolute 1.1% (SE = 0.5%) decrease in breast cancer mortality (4.8% for AI v 5.9% for tamoxifen; 2P = .1). Cohort 2 comprised 9,015 patients with a mean of 3.9 years of follow-up. At 3 years from treatment divergence (ie, approximately 5 years after starting hormonal treatment), AI therapy was associated with an absolute 3.1% (SE = 0.6%) decrease in recurrence (5.0% for AI v 8.1% for tamoxifen since divergence; 2P <.00001) and an absolute 0.7% (SE = 0.3%) decrease in breast cancer mortality (1.7% for AI v 2.4% for tamoxifen since divergence; 2P = .02). There was no convincing heterogeneity in the proportional recurrence reduction with respect to age, nodal status, tumor grade, or progesterone receptor status and no indication of an increase in nonbreast deaths with AIs in either cohort. Conclusion: AIs produce significantly lower recurrence rates compared with tamoxifen, either as initial monotherapy or after 2 to 3 years of tamoxifen. Additional follow-up will provide clearer information on long-term survival.

Original languageEnglish
Pages (from-to)509-518
Number of pages10
JournalJournal of Clinical Oncology
Volume28
Issue number3
DOIs
Publication statusPublished - Jan 20 2010

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Dowsett, M., Cuzick, J., Ingle, J., Coates, A., Forbes, J., Bliss, J., Buyse, M., Baum, M., Buzdar, A., Colleoni, M., Coombes, C., Snowdon, C., Gnant, M., Jakesz, R., Kaufmann, M., Boccardo, F., Godwin, J., Davies, C., & Peto, R. (2010). Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. Journal of Clinical Oncology, 28(3), 509-518. https://doi.org/10.1200/JCO.2009.23.1274