American Journal of Epidemiology Advance Access originally published online on March 27, 2008
American Journal of Epidemiology 2008 167(10):1207-1216; doi:10.1093/aje/kwn044
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ORIGINAL CONTRIBUTIONS |
Estrogen Plus Progestin Therapy and Breast Cancer in Recently Postmenopausal Women
1 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA
2 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA
3 Stanford Prevention Research Center, School of Medicine, Stanford University, Stanford, CA
4 Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
5 Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI
6 Department of Medicine, University of California, Irvine, CA
7 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
8 Department of Preventive Medicine, State University of New York, Stony Brook, NY
9 Department of Obstetrics and Gynecology, University of Miami, Miami, FL
10 National Heart, Lung, and Blood Institute, Bethesda, MD
Correspondence to Dr. Ross L. Prentice, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P.O. Box 19024, Seattle, WA 98109-1024 (e-mail: rprentic{at}fhcrc.org).
Received for publication July 13, 2007. Accepted for publication February 7, 2008.
The Women's Health Initiative trial found a modestly increased risk of invasive breast cancer with daily 0.625-mg conjugated equine estrogens plus 2.5-mg medroxyprogesterone acetate, with most evidence among women who had previously received postmenopausal hormone therapy. In comparison, observational studies mostly report a larger risk increase. To explain these patterns, the authors examined the effects of this regimen in relation to both prior hormone therapy and time from menopause to first use of postmenopausal hormone therapy ("gap time") in the Women's Health Initiative trial and in a corresponding subset of the Women's Health Initiative observational study. Postmenopausal women with a uterus enrolled at 40 US clinical centers during 1993–1998. The authors found that hazard ratios agreed between the two cohorts at a specified gap time and time from hormone therapy initiation. Combined trial and observational study data support an adverse effect on breast cancer risk. Women who initiate use soon after menopause, and continue for many years, appear to be at particularly high risk. For example, for a woman who starts soon after menopause and adheres to this regimen, estimated hazard ratios are 1.64 (95% confidence interval: 1.00, 2.68) over a 5-year period of use and 2.19 (95% confidence interval: 1.56, 3.08) over a 10-year period of use.
breast neoplasms; clinical trials as topic; cohort studies; estrogens; hormone replacement therapy; postmenopause; progestins
Abbreviations: CI, confidence interval; E+P, estrogen plus progestin; HT, postmenopausal hormone therapy; WHI, Women's Health Initiative
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