DES Daughters and Breast Cancer Risk

Prenatal Diethylstilbestrol Exposure and Risk of Breast Cancer

2006 Study Abstract

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.

DES Follow-up Study

One of the main purposes of our study is to examine whether prenatal DES exposure influences risk of breast cancer or other cancers in addition to cancers of the vagina and cervix. Results from our most recent analysis of prenatal DES exposure and breast cancer were published in the scientific journal Cancer Epidemiology Biomarkers and Prevention.

Questionnaire data collected in 2001, 1997, and 1994 were used to examine this issue among daughters participating in the study. 4,817 study participants whose mothers took DES while pregnant with them were compared with 2,073 participants who were unexposed. Medical records were obtained to confirm cancer diagnoses. A total of 102 participants were diagnosed with invasive breast cancer. Comparisons of exposed and unexposed women took into account differences in age and other factors such as number of births, age at first birth, and age at first menstruation that are related to breast cancer risk.

Before age 40, women exposed to DES prenatally were not at higher breast cancer risk compared to unexposed women. However, at ages 40 and older, DES-exposed women had two times the breast cancer risk of unexposed women. It appeared that the increase for exposed relative to unexposed women continued to rise with increasing age, but most study participants were still under 50 when the last questionnaire was completed and it is too early for definitive results. Data from the 2006 follow-up questionnaire will provide better information on this question. The association of DES exposure with breast cancer risk was present regardless of whether a participant had a family history of breast cancer or had used female hormone supplements.

Although breast cancer is the most common cancer in U.S. women, most women will never develop breast cancer. That is still the case for women exposed to DES prenatally – most will never develop breast cancer. Based on U.S. cancer registry data, for every 1,000 DES-exposed women aged 45-49, we would expect 4 new cases of breast cancer each year, compared to 2 new cases per year in 1,000 unexposed women.

Under American Cancer Society recommendations, all women who are 40 years or older are advised to undergo yearly mammograms to screen for early breast cancers. Women who were exposed to DES should follow this screening guideline if they are not already doing so.



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