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Cancer Risk in Women Exposed to Diethylstilbestrol In Utero
Elizabeth E. Hatch, PhD;
Julie R. Palmer, ScD;
Linda Titus-Ernstoff, PhD;
Kenneth L. Noller, MD;
Raymond H. Kaufman, MD;
Robert Mittendorf, MD, DrPh;
Stanley J. Robboy, MD;
Marianne Hyer, MS;
Charise M. Cowan;
Ervin Adam, MD;
Theodore Colton, ScD;
Patricia Hartge, ScD;
Robert N. Hoover, MD, ScD
JAMA. 1998;280:630-634.
Context.— The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero.
Objective.— To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up.
Design.— A cohort study with mailed questionnaires and medical record review of reported cancer outcomes.
Participants.— A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s.
Main Outcome Measures.— Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters.
Results.— To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result.
Conclusions.— Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.
From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md (Drs Hatch, Hartge, and Hoover); Slone Epidemiology Unit, Boston University School of Public Health, Boston, Mass (Drs Palmer and Colton); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (Dr Titus-Ernstoff); Department of Obstetrics and Gynecology, University of Massachusetts Medical Center, Worcester (Dr Noller); Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Tex (Drs Kaufman and Adam); Department of Obstetrics and Gynecology, University of Chicago, Chicago, Ill (Dr Mittendorf and Ms Cowan); Departments of Pathology and Obstetrics and Gynecology, Duke University Medical Center, Durham, NC (Dr Robboy); and Information Management Services, Rockville, Md (Ms Hyer).
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