Influence of exogenous estrogens, proliferative breast disease, and other variables on breast cancer risk

The authors reevaluated 10,366 consecutive breast biopsy specimens of benign lesions performed between 1950 and 1968. Follow-up information was obtained on 3303 women with a median duration of follow-up of 17 years. This sample contained 84% of the patients originally selected for follow-up. The relative risk (RR) of developing breast cancer was 0.98 for women who took exogenous estrogens as compared to 1.8 for women who did not. Exogenous estrogens lowered the observed breast cancer risk in women with atypical hyperplasia (RR = 3.0 versus 4.5), proliferative disease without atypia (RR = 0.92 versus 1.9), and in women without proliferative disease (RR = 0.69 versus 0.91). Women who took estrogens before 1956 were at 2.3 times the risk of other estrogen users, presumably due to a dose effect. There was no significant association between breast cancer risk and birth control pills, cigarette smoking, or alcohol consumption. Exogenous estrogens are not associated with increased breast cancer risk in women with benign breast disease. A previous history of benign breast disease does not contraindicate replacement estrogen therapy.