American Journal of Epidemiology Advance Access published online on April 29, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn089
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Invited Commentary: Postmenopausal Unopposed Estrogen and Breast Cancer Risk in the Women's Health Initiative—Before and Beyond
From the Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
Correspondence to Dr. Martha S. Linet, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS Room 7048, Bethesda, MD 20892-7238 (e-mail: linetm{at}mail.nih.gov).
Received for publication January 8, 2008. Accepted for publication March 11, 2008.
Three large clinical trials provoked major debate when hormone replacement therapy (HRT) did not reduce coronary heart disease in postmenopausal women as expected from observational epidemiologic studies. Less discussion has ensued about breast cancer or other adverse events. In this issue of the Journal, investigators from the Women's Health Initiative (WHI) compare breast cancer findings from the randomized trial of unopposed estrogen with those from the large WHI observational study. This commentary briefly summarizes historical highlights of menopausal hormone use; risk-versus-benefit evaluations; scientific, clinical, and policy influences immediately before and during the WHI trial; breast cancer incidence trends; and the posttrial response in US clinical practice. Factors complicating interpretation of the results include differences in breast cancer risk profiles between women in the trial and those in the observational study cohort as well as heterogeneity in the definitions of menopause and prior use of HRT as applied by the WHI investigators to the two populations. Because millions of women use HRT, it is important to consider how the WHI and other research investigations might contribute to reducing gaps in understanding the relation between HRT and breast cancer risk.
breast neoplasms; clinical trial; epidemiologic studies; estrogens; hormone replacement therapy; menopause; risk-benefit assessment
Abbreviations: HRT, hormone replacement therapy; WHI, Women's Health Initiative