Cancer incidence in women exposed to DES in utero

Purpose Diethylstilbestrol (DES), a synthetic estrogen administered to millions of women in the U.S. and Europe, was shown in the early 1970s to have a strong association with clear cell adenocarcinoma (CCA) in the daughters who were exposed in utero. Results from data collected through 1994 from the NCI DES Combined Cohorts Follow-up Study showed that DES-exposed daughters experienced no excess risk of all cancers combined in comparisons with both the general population and daughters who were unexposed to DES. Except for CCA, for which a strong association was demonstrated, risk in exposed daughters was not elevated for individual cancer sites. Data through 1997 suggested, however, that DES is associated with an elevated breast cancer risk in women 40 years of age and older. Methods Preliminary analysis of new cases reported through 2001 compared observed to expected cancer rates based upon age- and calendar-year specific SEER incidence rates in white females. Standardized incidence ratios (SIR) with 95% confidence intervals were calculated. Results A total of 235 cancer cases occurred during follow up, with 175 occurring among exposed women (97,830 person-years) and 60 among unexposed women (34,810). Overall, there was no excess risk of cancer among DES-exposed daughters for all cancers combined (SIR 1.1; 95% CI 0.91–1.2), or among the unexposed comparison group (SIR 0.86; 95% CI 0.67–1.1). One new case of CCA of the cervix/vagina occurred since the 1994 follow up for a total of four confirmed cases of CCA in the exposed with less than 0.1 expected resulting in a SIR of 41 (95% CI 15–110), and no cases occurring in the unexposed women. Conclusions Data addressing the association of DES and cancer risk in daughters updated with 7 additional years of follow-up will be presented. Specific results for cancer sites will be discussed in the context of the in utero estrogen exposure hypothesis and subsequent cancer risk.