Exogenous estrogen and breast cancer after bilateral oophorectomy

Estrogen use in 119 women in whom breast cancer developed after surgically induced menopause was compared to use among an equal number of controls matched for age, date of bilateral oophorectomy, and duration of follow-up. No increased risk for estrogen use versus no use was evident (relative risk = 0.7). When the authors examined three measures of estrogen dose--number of chart notations of estrogen use, time since first use, and duration between first and last use--only those with greater than or equal to 5 notations had any significantly elevated risk (relative risk = 2.1; confidence limits 1.2-3.6), and there was a significant trend toward increasing risk with more notations (P = 0.03). Use specifically of conjugated estrogens was also associated with an increasing risk with more notation of estrogen use (P = 0.07). However, the other two measures of dose did not confirm this trend. Matched multiple logistic analysis suggested that number of notations of estrogen use conferred increased breast cancer risk (relative risk = 1.7), in dose-response relationships, but this result could have occurred by chance. Because of a lack of consistency, the generally low and statistically nonsignificant relative risks, and the lack of consistent effect modification in high-risk groups, the authors were unable to demonstrate a clear increased risk of breast cancer associated with replacement estrogen use.