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Karen K. Steinberg, PhD, MSc; Stephen B. Thacker, MD, MSc; S. Jay Smith, MS, MIS; Donna F. Stroup, PhD, MSc; Matthew M. Zack, MD; W. Dana Flanders, MD, DSc; Ruth L. Berkelman, MD

JAMA. 1991;265(15):1985-1990.

Abstract
To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7).

(JAMA. 1991;265:1985-1990)

Author Affiliations
From the Center for Environmental Health and Injury Control (Dr Steinberg and Mr Smith), Epidemiology Program Office (Drs Thacker and Stroup), Center for Chronic Disease Prevention and Health Promotion (Dr Zack), and Center for Infectious Disease (Dr Berkelman), Centers for Disease Control, Atlanta, Ga; and School of Public Health, Emory University, Atlanta, Ga (Dr Flanders).

Footnotes
Use of trade names is for identification only and does not constitute endorsement by the Public Health Service or the US Department of Health and Human Services.

Reprint requests to Center for Environmental Health and Injury Control, Centers for Disease Control, MS F-18,1600 Clifton Rd, Atlanta, GA 30333 (Dr Steinberg).

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