DES Daughters and Breast Cancer

Risk of breast cancer in women exposed to diethylstilbestrol in utero: prelimiinary results (United States), 2002

Abstract

BACKGROUND
A synthetic estrogen, diethylstilbestrol (DES), was widely prescribed to pregnant women during the 1950s and 1960s but was later discovered to be associated with an increased risk of clear-cell carcinoma of the vagina and cervix in female offspring. DES has not been linked to other cancers in female offspring, but studies of other prenatal factors such as twin gestation and pre-eclampsia have indicated that in-utero estrogen levels may influence breast cancer risk. We evaluated the relation of in-utero DES exposure to the risk of adult breast cancer.

METHODS
A cohort of 4821 exposed women and 2095 unexposed women, most of whom were first identified in the mid-1970s, were followed by mailed questionnaires for an average of 19 years. Reported cancer outcomes were validated by medical record review. Breast cancer incidence in DES-exposed daughters was compared with cancer incidence in unexposed daughters with use of Poisson regression analysis, adjusting for year of birth, age at menarche, age at first birth, and number of births.

FINDINGS
The rate ratio for incidence of invasive breast cancer in exposed versus unexposed women was 1.4 (95% confidence interval (CI) = 0.7-2.6). DES exposure was not associated with an increased risk of breast cancer in women under 40 years, but among women aged 40 and older the rate ratio was 2.5 (95% CI = 1.0-6.3). The rate ratio for the association of DES exposure with estrogen receptor-positive tumors was 1.9 (95% CI = 0.8-4.5).

INTERPRETATION
While not statistically significant, the overall 40% excess risk, arising exclusively from the subset of estrogen receptor-positive cases, raises a concern calling for continued investigation.

DES Follow-up Study

The question of whether daughters of women who took DES while pregnant with them will have a greater chance of getting breast cancer has been of great interest to both the DES population and researchers. Questionnaire data collected in 1994 and 1997 from participants in the combined follow-up study were used to investigate this question. 4821 exposed and 2095 unexposed women completed one or both of the follow-up questionnaires, answering questions on reproductive factors, health habits, and disease outcomes. Reports of breast cancer were confirmed by checking medical records or death certificates. There were 43 cases of breast cancer among the DES-exposed and 15 among the unexposed women.

Overall, exposed daughters did not have a statistically significant increase in the risk of breast cancer. Although the relative risk was 1.4, this elevation could have been a chance finding due to the small number of breast cancer cases. However, among the subgroup of women aged 40 and older, those exposed to DES were estimated to have 2.5 times the risk of breast cancer, and this result was statistically significant. Follow-up in the study has continued, and a new analysis that includes additional cases diagnosed since 1997 has begun. The new analysis will likely provide more definitive results.

Sources

DES DIETHYLSTILBESTROL RESOURCES

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