Objective: In postmenopausal black women in the Women's Health Initiative randomized trial, estrogen alone reduced breast cancers but its comprehensive influence on health outcomes in black women is unknown. Therefore, we examined this issue in the Women's Health Initiative overall and by African ancestry.
Methods: A total of 1,616 black women with prior hysterectomy, including 1,061 with percent African ancestry determination, at 40 US centers were randomly assigned to conjugated equine estrogen (0.625 mg/d) or placebo for 7.2 years’ (median) intervention with 13 years’ cumulative follow-up. Coronary heart disease (CHD) and breast cancer were primary efficacy and safety outcomes, respectively. A global index also included stroke, colorectal cancer, hip fracture, pulmonary embolism, and death.
Results: Black women in the estrogen-alone group compared with black women in the placebo group had fewer breast cancers (17 vs 40, hazard ratio [HR] 0.47, 95% CI 0.26-0.82). In women with more than 80% African ancestry, breast cancer HR was lower (0.32, 95% CI 0.12-0.86, trend P = 0.04 for ancestry effect). Most other outcomes including CHD, stroke, hip fracture, and the global index were null with estrogen use in black women; a global index effect was more favorable in younger black women (HR 0.65, 95% CI 0.43-0.98).
Conclusions: In black postmenopausal women with prior hysterectomy, estrogen alone significantly reduced breast cancer incidence with no adverse influence on CHD, venous thromboembolism, or all-cause mortality. Favorable estrogen-alone global index effects in younger black women warrant further study.
1Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA
2Division of Public Health Issues, Fred Hutchinson Cancer Research Center, Seattle, WA
3Brigham and Women's Hospital, Harvard Medical School, Boston, MA
4School of Medicine and Public Health, University of Wisconsin, Madison, WI
5Department of Obstetrics and Gynecology, University of Miami, Miami, FL
6Harbor-UCLA Medical Center, Department of Medicine, Torrance, CA
7School of Public Health, University of Pittsburgh, Pittsburgh, PA
8Division of Biostatistics, School of Medicine, University of California, Davis, CA
9College of Public Health, University of Iowa, Iowa City, IA.
Address correspondence to: Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1024 W. Carson Street, Building N16, Torrance, CA 90501. E-mail: firstname.lastname@example.org
Received 10 April, 2016
Revised 11 July, 2016
Accepted 11 July, 2016
R.T.C. and A.K.A. had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: R.T.C., W.B., J.E.M., M.J.O., R.L.W., and R.L.P. Acquisition of data: R.T.C., J.E.M., G.S., M.J.O., J.A.C., R.L.W., L.Q., and R.L.P. Analysis and interpretation of data: R.T.C., W.B., A.K.A., J.E.M., G.S., M.J.O., L.Q., G.S., M.J.O., D.W., J.A.C., R.L.W., and R.L.P. Drafting of the manuscript: R.T.C. Critical revision of the manuscript for important intellectual content: R.T.C., W.B., A.K.A., J.E.M., M.J.O., D.W., J.A.C., L.Q., R.L.W., and R.L.P. Administrative, technical, or material support: R.T.C., J.E.M., M.J.O., J.A.C., R.L.W., and R.L.P.
These data have been previously published in oral abstract format at the ASCO Annual Meeting in Chicago, IL, May 29 to June 2, 2015. These data and results, however, have not been previously published in manuscript format.
Funding/support: The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute at the National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 321115, 32118-32119, 32122, 42107-26, 42129-32 and 44221. Wyeth-Ayerst donated the study drugs.
Clinical trial registration: clinical trials.gov Identifier: NCT00000611.
Financial disclosure/conflicts of interest: R.T.C. reported receiving consulting fees or honoraria from Novartis, Amgen, Genentech, and Genomic Health; fees for participation in review activities for Pfizer and Novo Nordisk; payment for lectures from Novartis and Genentech; and payment for educational activities from Educational Concepts Group. No other authors have conflicts of interest.