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

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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.

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Authors and Affiliations

  1. Slone Epidemiology Unit, Boston University School of Medicine, Boston, MA, USA

    Julie R. Palmer & R. Sowmya Rao

  2. Slone Epidemiology Unit, Boston University School of Medicine, 1010 Commonwealth Avenue, Boston, MA, 02215, USA

    Julie R. Palmer

  3. Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA, USA

    Elizabeth E. Hatch & Theodore Colton

  4. Section of Hematology and Oncology, Boston University School of Medicine, Boston, MA, USA

    Carol L. Rosenberg

  5. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Patricia Hartge, Rebecca Troisi & Robert N. Hoover

  6. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA

    Raymond H. Kaufman

  7. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    Linda Titus-Ernstoff

  8. Department of Obstetrics and Gynecology, New England Medical Center, Boston, MA, USA

    Kenneth L. Noller

  9. Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, USA

    Arthur L. Herbst

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  1. Julie R. Palmer
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  2. Elizabeth E. Hatch
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  3. Carol L. Rosenberg
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  4. Patricia Hartge
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  5. Raymond H. Kaufman
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  6. Linda Titus-Ernstoff
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  7. Kenneth L. Noller
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  8. Arthur L. Herbst
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  9. R. Sowmya Rao
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  10. Rebecca Troisi
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  11. Theodore Colton
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  12. Robert N. Hoover
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Palmer, J.R., Hatch, E.E., Rosenberg, C.L. et al. Risk of breast cancer in women exposed to diethylstilbestrol in utero: preliminary results (United States). Cancer Causes Control 13, 753–758 (2002). https://doi.org/10.1023/A:1020254711222

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  • DOI: https://doi.org/10.1023/A:1020254711222

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