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1 Slone Epidemiology Center and 2 Department of Epidemiology, Boston University School of Public Health; 3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; 4 Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire; 5 Department of Obstetrics and Gynecology, New England Medical Center, Boston, Massachusetts; 6 Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 7 Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois; and 8 Information Management Services, Rockville, Maryland
Requests for reprints: Julie R. Palmer, Slone Epidemiology Center, Boston University, 1010 Commonwealth Avenue, Boston, MA 02215. Phone: 617-734-6006; Fax: 617-738-5119. E-mail: jpalmer{at}slone.bu.edu
It has been hypothesized that breast cancer risk is influenced by prenatal hormone levels. Diethylstilbestrol (DES), a synthetic estrogen, was widely used by pregnant women in the 1950s and 1960s. Women who took the drug have an increased risk of breast cancer, but whether risk is also increased in the daughters who were exposed in utero is less clear. We assessed the relation of prenatal DES exposure to risk of breast cancer in a cohort of DES-exposed and unexposed women followed since the 1970s by mailed questionnaires. Eighty percent of both exposed and unexposed women completed the most recent questionnaire. Self-reports of breast cancer were confirmed by pathology reports. Cox proportional hazards regression was used to compute incidence rate ratios (IRR) for prenatal DES exposure relative to no exposure. During follow-up, 102 incident cases of invasive breast cancer occurred, with 76 among DES-exposed women (98,591 person-years) and 26 among unexposed women (35,046 person-years). The overall age-adjusted IRR was 1.40 [95% confidence interval (95% CI), 0.89-2.22]. For breast cancer occurring at ages 
40 years, the IRR was 1.91 (95% CI, 1.09-3.33) and for cancers occurring at ages 50 years, it was 3.00 (95% CI, 1.01-8.98). Control for calendar year, parity, age at first birth, and other factors did not alter the results. These results, from the first prospective study on the subject, suggest that women with prenatal exposure to DES have an increased risk of breast cancer after age 40 years. The findings support the hypothesis that prenatal hormone levels influence breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1509–14)
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