Prenatal diethylstilbestrol exposure and risk of benign breast disease: The National Cancer Institute Diethylstilbestrol Follow-up Study.

Prenatal exposure to diethylstilbestrol (DES), a prototypical endocrine disruptor, has been associated with increased breast cancer risk after age 40. We assessed the association between prenatal DES exposure and self-reported benign breast disease (BBD)-an established breast cancer risk factor-among 4208 DES-exposed and 1830 unexposed women in the National Cancer Institute DES Follow-up Study. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Follow-up started at birth and ended at the earliest of: BBD, breast cancer diagnosis, death, or loss to follow-up. We estimated cumulative incidence of BBD by DES exposure. Over the course of the study, 6038 women contributed 333,458 person-years with median follow-up of 43.0 (range: 13.8-74.0) years for 1089 BBD cases and 60.0 (range: 19.7-80.3) years for 4949 non-cases. Comparing BBD rates among DES-exposed with unexposed women, the HR was 0.97 (95% CI: 0.84, 1.11), with no evidence of a dose-response relationship or difference in cumulative incidence by exposure. In conclusion, the HR for BBD was not elevated among women who were prenatally exposed to DES, suggesting that observed increases in breast cancer risk associated with DES are not due to this pathological mechanism.