The Use of Estrogens and Progestins and the Risk of Breast Cancer in Postmenopausal Women
Graham A. Colditz, M.B., B.S., Susan E. Hankinson, Sc.D., David J. Hunter, M.B., B.S., Walter C. Willett, M.D., JoAnn E. Manson, M.D., Meir J. Stampfer, M.D., Charles Hennekens, M.D., Bernard Rosner, Ph.D., and Frank E. Speizer, M.D.
Background The effect of adding progestins to estrogen therapyon the risk of breast cancer in postmenopausal women is controversial.
Methods To quantify the relation between the use of hormonesand the risk of breast cancer in postmenopausal women, we extendedour follow-up of the participants in the Nurses' Health Studyto 1992. The women were asked to complete questionnaires everytwo years to update information on their menopausal status,use of estrogen and progestin preparations, and any diagnosisof breast cancer. During 725,550 person-years of follow-up,we documented 1935 cases of newly diagnosed invasive breastcancer.
Results The risk of breast cancer was significantly increasedamong women who were currently using estrogen alone (relativerisk, 1.32; 95 percent confidence interval, 1.14 to 1.54) orestrogen plus progestin (relative risk, 1.41; 95 percent confidenceinterval, 1.15 to 1.74), as compared with postmenopausal womenwho had never used hormones. Women currently taking hormoneswho had used such therapy for 5 to 9 years had an adjusted relativerisk of breast cancer of 1.46 (95 percent confidence interval,1.22 to 1.74), as did those currently using hormones who haddone so for a total of 10 or more years (relative risk, 1.46;95 percent confidence interval, 1.20 to 1.76). The increasedrisk of breast cancer associated with five or more years ofpostmenopausal hormone therapy was greater among older women(relative risk for women 60 to 64 years old, 1.71; 95 percentconfidence interval, 1.34 to 2.18). The relative risk of deathdue to breast cancer was 1.45 (95 percent confidence interval,1.01 to 2.09) among women who had taken estrogen for five ormore years.
Conclusions The addition of progestins to estrogen therapy doesnot reduce the risk of breast cancer among postmenopausal women.The substantial increase in the risk of breast cancer amongolder women who take hormones suggests that the trade-offs betweenrisks and benefits should be carefully assessed.
Source Information
From the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (G.A.C., S.E.H., D.J.H., W.C.W., J.E.M., M.J.S., C.H., B.R., F.E.S.), and the Departments of Epidemiology (G.A.C., S.E.H., D.J.H., W.C.W., M.J.S.), Biostatistics (B.R.), and Nutrition (W.C.W., M.J.S.), Harvard School of Public Health — all in Boston. Presented in part at the meeting of the American Association for the Advancement of Science, San Francisco, February 22, 1994.
Address reprint requests to Dr. Colditz at Harvard Medical School, Channing Laboratory, 180 Longwood Ave., Boston, MA 02115.
Breast Cancer and Hormone-Replacement Therapy
Brunoski T., Powell L. H., Blackman J. A., Bush T. L., Joseph K.S., Dupont W. D., Wigg D.R., Bluming A. Z., Colditz G. A., Willett W. C., Speizer F. E.
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N Engl J Med 1995;
333:1355-1358, Nov 16, 1995.
Correspondence
Postmenopausal Hormone Therapy and Mortality
Whooley M. A., Grady D., Cummings S. R., Green J., Wintfeld N., Atkins C. D., Grodstein F., Stampfer M. J., Willett W. C.
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N Engl J Med 1997;
337:1389-1391, Nov 6, 1997.
Correspondence
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A correction has been published: N Engl J Med 1995;333(20):1355.
