Prenatal Diethylstilbestrol Exposure and Risk of Breast Cancer

Palmer, Julie R.; Wise, Lauren A.; Hatch, Elizabeth E.; Troisi, Rebecca; Titus-Ernstoff, Linda; Strohsnitter, William C.; Kaufman, Raymond H.; Herbst, Arthur L.; Noller, Kenneth L.; Hyer, Marianne; Hoover, Robert N.

doi:10.1158/1055-9965.epi-06-0109

Cited by 317 publications

(250 citation statements)

References 36 publications

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“…4 More recent follow-up of the cohort for breast cancer incidence has shown a small but progressively increasing risk for DES exposure with age after 40. 5,6 To date, the follow-up experience of the combined cohort with regard to overall and reproductive tract cancer risk has not been characterized. During the 7 years of follow-up that have elapsed since the baseline survey, nearly 42,000 additional woman years have accrued, and the number of reported cases has more than doubled.…”

mentioning

confidence: 99%

Cancer risk in women prenatally exposed to diethylstilbestrol

Troisi

Hatch

Titus-Ernstoff

et al. 2007

Intl Journal of Cancer

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158

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Prenatal diethylstilbestrol (DES) exposure is associated with excess risks of clear cell adenocarcinoma (CCA), and breast cancer in older women. Whether overall cancer risk is also elevated is unclear. Total and site-specific cancer risks were evaluated in the DES Combined Cohort Follow-up Study using age-and calendaryear specific standardized incidence rate ratios (SIR), and ageadjusted incidence rate ratios (RR) comparing DES exposed and unexposed women. A total of 143 and 49 cancer cases occurred in 97,831 and 34,810 person-years among the exposed and unexposed, respectively. There was no overall excess risk among exposed women when compared with external rates (SIR 1.01; 95% confidence interval [CI] 0.86-1.2). The overall RR comparing exposed with unexposed women was 1.32 (95% CI 0.94-1.8). Breast cancer risk was elevated only among women over 40 years (RR 1.83; 95% CI 1.1-3.2). The CCA SIR among exposed women was nearly 40, and the estimated attack rate through age 39 was 1.6/1,000 women. CCA incidence decreased by over 80% after age 25 when compared with 20-24 years. Excluding CCA and breast cancer, the overall RR was 1.21 (95% CI 0.74-2.0). DES was not associated with excess risks of either endometrial or ovarian cancer. These data suggest that the DES associated increase in CCA incidence remains elevated through the reproductive years. There was no consistent evidence of risk excesses for cancers other than CCA, and breast cancer in older women. Given that the population is still young, continued follow-up is necessary to assess the overall carcinogenic impact of prenatal DES exposure. ' 2007 Wiley-Liss, Inc.Key words: diethylstilbestrol; estrogen; cancer Diethylstilbestrol (DES), a potent synthetic estrogen, was first synthesized in 1938 and shortly thereafter promoted to prevent spontaneous abortion and premature delivery. 1 Over the next three decades, DES was administered to several million pregnant women in the United States and Europe. In 1971, a strong association was reported between DES and clear cell adenocarcinoma (CCA) of the vagina and cervix in young women. 2 Animal studies suggest the teratogenic and carcinogenic effects of prenatally administered DES may be due to changes in the expression of genes involved in the development of the reproductive tract 3 and raise concerns of elevated risk of other female reproductive tract cancers besides CCA.In the early 1990s, the National Cancer Institute (NCI) assembled new and previously established cohorts of DESexposed and unexposed individuals for combined follow-up. Baseline findings limited to analysis of the previously established cohorts showed DES was associated with an excess CCA risk and possibly with elevated breast cancer risk in older women, but did not indicate greater risk of endometrial or ovarian cancer. 4 More recent follow-up of the cohort for breast cancer incidence has shown a small but progressively increasing risk for DES exposure with age after 40. 5,6 To date, the follow-up experience of the combined cohort with regard to ove...

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mentioning

confidence: 99%

Cancer risk in women prenatally exposed to diethylstilbestrol

Troisi

Hatch

Titus-Ernstoff

et al. 2007

Intl Journal of Cancer

Self Cite

158

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“…The 2006 report confirmed that the increased risk of breast cancer among the second generation was discernible after the age of 40 and found out that the risk was then increased with age. Furthermore, a significant dose-response was also deduced (Palmer et al, 2006). The 2011 follow up report on the same NCI cohort supported these findings especially the dose-response relationship which was established through its surrogate marker ,vaginal epithelial changes, in the 2011 report as compared to the less robust calculations of the 2006 report (Hoover et al, 2011).…”

Section: Synthetic Estrogens: the Tragedy Of Diethylstilbestrol (Des)mentioning

confidence: 77%

“…The 2011 follow up report on the same NCI cohort supported these findings especially the dose-response relationship which was established through its surrogate marker ,vaginal epithelial changes, in the 2011 report as compared to the less robust calculations of the 2006 report (Hoover et al, 2011). Collectively, the available data support a causal relationship between DES exposure during pregnancy and breast cancer risk among daughters and should have clinical implications for these women as the authors suggested (Palmer et al, 2006;Hoover et al, 2011). Moreover, studies of the third generation might be justified to find out whether or not DES exposure could exert transgenerational epigenetic effect (Skinner et al, 2011).…”

Section: Synthetic Estrogens: the Tragedy Of Diethylstilbestrol (Des)mentioning

confidence: 87%

Endocrine Disruptors and Breast Cancer Risk - Time to Consider the Environment

Abdel‐Rahman

Moustafa²,

Ahmed³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…The latest results suggest that the DES daughters also have an increased risk of breast cancer after age 40 years (Palmer et al 2006). Even the fertility of men exposed to DES has been investigated, but revealed that there was no increased risk of infertility among men exposed to DES before birth (Wilcox et al 1995).…”

Section: Examination Of the Supplementmentioning

confidence: 99%

Gynaecomastia linked to the intake of a herbal supplement fortified with diethylstilbestrol

Toorians

Bovee

Rooy

et al. 2010

Food Additives & Contaminants: Part A

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This study reports the findings of a supplement marketed on the internet for prostate problems. The supplement was orally taken by a 60-year old man with divergent hormonal levels and who was surgically treated for gynaecomastia: development of abnormally large mammary glands in males. The supplement showed a strong effect in a yeast estrogen bioassay, expressing a yeast enhanced green fluorescent protein (yEGFP) upon exposure to estrogens. Using both NMR and a gradient liquid chromatographic time of flight mass spectrometric (LC/TOFMS) method, the response was shown to be caused by very high levels of diethylstilbestrol, known for causing gynaecomastia. The gynaecomastia was most probably caused by this orally taken 'natural' herbal supplement, as the patient hormonal levels also returned to normal again when stopping the use of it. This case demonstrates that physicians need to be aware of the use of supplements with illegal components that may be responsible for unwanted side-effects.

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Prenatal Diethylstilbestrol Exposure and Risk of Breast Cancer

Cited by 317 publications

References 36 publications

Cancer risk in women prenatally exposed to diethylstilbestrol

Cancer risk in women prenatally exposed to diethylstilbestrol

Endocrine Disruptors and Breast Cancer Risk - Time to Consider the Environment

Gynaecomastia linked to the intake of a herbal supplement fortified with diethylstilbestrol

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