Breast cancer in mothers prescribed diethylstilbestrol in pregnancy, 1993 further follow-up

Further assessment of the long-term risk of breast cancer associated with DES during pregnancy

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Contrary to prior indications, the modest but statistically significant increased risk of breast cancer does not appear to increase greatly over time. Image via Hernán Piñera.

1993 Study Abstract

OBJECTIVE:
Further assessment of the long-term risk of breast cancer associated with diethylstilbestrol (DES) during pregnancy.

DESIGN:
Follow-up continuation through June 1, 1989, of a historical cohort of DES-exposed and unexposed mothers ascertained by review of obstetric records.

PARTICIPANTS:
Totals of 3029 each of DES-exposed and unexposed mothers who had delivered live babies at four centers in the United States during 1940 through 1960. Questionnaires were returned for 92.6% of the DES-exposed and 88.8% of the unexposed women.

MAIN OUTCOME MEASURES:
Breast cancer incidence and mortality assessed from returned questionnaires and review of medical records and death certificates.

MAIN RESULTS:
The relative rate of breast cancer associated with DES exposure, after adjustment for demographic and reproductive variables, was 1.35 (95% confidence interval, 1.05 to 1.74). For 30 years or more following exposure, the relative rate was not appreciably higher (relative rate, 1.33; 95% confidence interval, 0.95 to 1.87) than that in earlier periods. Surveillance and increased detection seemed unlikely explanations for the increased risk, since DES-exposed women had excesses of both large and small breast cancers and the two cohorts reported similar breast cancer detection practices. A history of miscarriage before first term delivery was not associated with breast cancer occurrence.

CONCLUSION:
Exposure to DES during pregnancy is associated with a modest but statistically significant increased risk of breast cancer. Contrary to prior indications, the risk does not appear to increase greatly over time. The findings are sufficient to exclude the possibility of a doubling of risk for the period of 30 or more years following exposure.

Sources
  • Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up., Colton T1, Greenberg ER, Noller K, Resseguie L, Van Bennekom C, Heeren T, Zhang Y. NCBI PMID: 8468763. 1993 Apr 28;269(16):2096-100.
  • Full text, JAMA, 1993;269(16):2096-2100. doi:10.1001/jama.1993.03500160066033, April 28, 1993.
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Dysplasia and Cytologic Findings in 4589 Young Women enrolled in DiEthylStilbestrol-Adenosis Project

DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced

Abstract

image of PubMed NCBI The Endocrine Society logo
DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced.

This report presents the cytologic findings and the rates of dysplasia for 4,589 young women enrolled in the National Cooperative Diethylstilbestrol-Adenosis (DESAD) Project. Mucinous columnar cells and/or metaplastic squamous cells with or without mucinous droplets were encountered in 22% of vaginal scrape smears from all diethylstilbestrol (DES)-exposed participants identified by review of prenatal records and in 43% of women in whom vaginal epithelial changes (VEC) were observed by colposcopy or by iodine staining. The frequency of cellular findings in the vaginal scrape smears was closely related to the timing of the administration of the DES to the mother. With increasing age of the daughters, the overall frequencies of both the mucinous and metaplastic cells decreased; relative to each other, an increasing proportion was metaplastic squamous cells. These data suggest that, as the women grow older, vaginal adenosis regresses by the process of squamous metaplasia. Endometrial type cells were found in 2% of vaginal scrape smears. Their cyclical occurrence during the menstrual cycle and lack of correlation with the presence of VEC indicated an origin from the uterine corpus rather than the tuboendometrial type of adenosis. Squamous cell dysplasia of the vagina and cervix was detected by biopsy or scrape smear specimens in 1.8% of DES-exposed women in the record review group. The rate of unexposed women was twice as high. In general, the rates of dysplasia were higher in the cervix than vagina, and the more severe degrees of dysplasia were encountered only in those women who were referred to the DESAD Project or who themselves requested entry. Four patients who were referred or who themselves requested entry were found to have clear cell adenocarcinoma of the vagina. The vaginal smear provided the first clue to the presence of an abnormality in three of them.

Sources

  • Dysplasia and cytologic findings in 4,589 young women enrolled in diethylstilbestrol-adenosis (DESAD) project, NCBI, PMID: 7195652, Am J Obstet Gynecol. 1981 Jul 1;140(5):579-86.
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Effects on the Menstrual Cycle of in Utero Exposure to DiEthylStilbestrol

DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced

Abstract

image of PubMed NCBI The Endocrine Society logo
DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced for consumption.

OBJECTIVES:
The purpose of this study was to determine the effects of in utero exposure to diethylstilboestrol on the menstrual cycle.

STUDY DESIGN:
This was a prospective cohort study of 198 diethylstilbestrol-exposed women and 162 unexposed controls, recruited from women whose mothers participated in a randomized trial of diethylstilbestrol in pregnancy at the Chicago Lying-In Hospital from 1950 to 1952. Women with severe menstrual abnormality were excluded from the study.

RESULTS:
Diethylstilbestrol exposure was associated with a statistically significantly decreased duration of menstrual bleeding of approximately one half day and a lower average daily bleeding score (self-reported). We found no evidence for effects of diethylstilbestrol exposure on cycle length or variability of cycle length. Exposure was not related to symptoms of dysmenorrhea.

CONCLUSIONS:
The decreased duration and amount of menstrual bleeding among diethylstilbestrol-exposed women could be due to direct effects on the uterus. The lack of an effect on cycle length and variability appears to indicate that endocrine function is not grossly disturbed in those women studied.

Sources:
  • Effects on the menstrual cycle of in utero exposure to diethylstilbestrolNCBI, PMID: 8141188,
    Am J Obstet Gynecol. 1994 Mar;170(3):709-15.
  • Full text: American Journal of Obstetrics and Gynecology, S0002937894702683, DOI: 10.1016/S0002-9378(94)70268-3.
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A Twenty-Five-Year Follow-Up Study of Women exposed to DiEthylStilbestrol during Pregnancy

DES usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced

Abstract

image of PubMed NCBI The Endocrine Society logo
DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced for consumption.

To assess the long-term effects of diethylstilboestrol (DES) we conducted a health survey among 693 mothers who had taken the drug during pregnancy and a comparable group of 668 who had not. These women had participated in a study during 1951-52 to evaluate the drug. There were 32 (4.6 per cent) breast cancers among the 693 exposed and 21 (3.1 per cent) among the 668 unexposed, but the difference was not statistically significant (P = 0.16). No statistically significant differences occurred between the groups in any of the other categories of disease. The occurrence of breast cancer in both groups was compared to the Connecticut State Tumor Registry for 1963-65. Compared to the registry data, a significantly (P less than 0.01) higher incidence of breast cancer occurred in both the exposed and unexposed groups at ages over 50. The reason for this increase is not known, but effects linked to the selection of mothers participating in the original clinical study cannot be excluded.

Sources:
  • A twenty-five-year follow-up study of women exposed to diethylstilbestrol during pregnancy,
    NCBI, PMID: 628409, N Engl J Med. 1978 Apr 6;298(14):763-7.
  • Full text: NEJM, 197804062981403,
    N Engl J Med 1978; 298:763-767April 6, 1978DOI: 10.1056/NEJM197804062981403
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