Cancer Risk in Women Exposed to Diethylstilbestrol In Utero

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Abstract
DIETHYLSTILBESTROL (DES), a drug first synthesized in 1938,1 was administered to several million pregnant women in the United States and Europe for the prevention of spontaneous abortion and premature delivery.2 In 1971, Herbst et al3 reported a strong association between DES use in pregnancy and the occurrence of vaginal clear cell adenocarcinoma (CCA) in exposed female offspring. Animal models have demonstrated a range of DES effects on offspring exposed in utero, including reproductive dysfunction, immune system changes, behavioral and sexual abnormalities, and increases in various reproductive cancers in males and females. However, the applicability of these experiments to humans and the mechanism of carcinogenesis are unclear.4 In the mid-1970s, several separate cohorts of DES-exposed daughters and unexposed comparison groups were followed for the occurrence of cancer, precursor lesions, and reproductive effects,5-7 but systematic follow-up of these cohorts had ceased by 1990. Concern has arisen that DES-exposed daughters may be at higher risk of breast cancer.8 Exposure to high levels of endogenous estrogen in utero has been hypothesized to increase the risk of breast cancer9 and DES is a potent estrogen. We conducted a study to ascertain the risk of breast and other cancers in women exposed to DES in utero by combining the previously identified cohorts, beginning follow-up in 1978 and extending it through 1994.