Breast Cancer in Mothers Prescribed Diethylstilbestrol in Pregnancy

Colton, Theodore; Greenberg, E. Robert; Noller, Kenneth L.; Resseguie, Laurence J.; Bennekom, Carla Van; Heeren, Timothy; Zhang, Yuqing

doi:10.1001/jama.1993.03500160066033

Cited by 89 publications

(31 citation statements)

References 18 publications

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“…However, a study examining dose in relation to breast cancer risk found no evidence of dose response (Hadjimichael et al, 1984), and our previous study of breast cancer incidence in the combined cohort showed similar risks for WHS and Dieckmann women (Titus-Ernstoff et al, 2001). Some studies of breast cancer incidence, including two previous studies based on the WHS and Dieckmann cohorts, suggested possible latency effects (Bibbo et al, 1978;Colton et al, 1993), but others did not (Greenberg et al, 1984;Hadjimichael et al, 1984;Titus-Ernstoff et al, 2001), including a large study conducted in Connecticut (Hadjimichael et al, 1984). Consistent with previous reports (Hadjimichael et al, 1984;Calle et al, 1996), we found no evidence that breast cancer mortality differed according to time since exposure.…”

Section: Discussionmentioning

confidence: 99%

“…The WHS enrolled DES-exposed and unexposed women who were ascertained through a retrospective review of obstetrics records for the period 1940 -1960 at the Mayo Clinic in Rochester, MN; Mary Hitchcock Memorial Hospital in Hanover, NH; a pregnancy clinic at the Boston Lying-In Hospital, in Boston, MA; and a private obstetrics practice in Portland, ME (Greenberg et al, 1984;Colton et al, 1993;Titus-Ernstoff et al, 2001). Diethylstilbestrol-exposed women were those whose records indicated that DES (or, rarely, another nonsteroidal oestrogen) had been prescribed during at least one pregnancy resulting in a live birth.…”

Section: Methodsmentioning

confidence: 99%

“…Diethylstilbestrol was withdrawn from use during pregnancy in the early 1970s, after it was shown that in utero exposure was strongly associated with the risk of vaginal adenocarcinoma (Herbst et al, 1971). Until that time, as many as 2 million women in the US (Noller and Fish, 1974), and 4 million women worldwide (Newbold, 1993) were given DES during pregnancy.Most studies, but not all (Vessey et al, 1983), have suggested a positive association between DES taken during pregnancy and breast cancer incidence (Bibbo et al, 1978;Clark and Portier, 1979;Beral and Colwell, 1980;Greenberg et al, 1984;Hadjimichael et al, 1984;Colton et al, 1993;Titus-Ernstoff et al, 2001), although the latter four studies produced findings compatible with chance. Of the studies assessing DES in relation to breast cancer mortality, one observed a significant association (Calle et al, 1996); four produced suggestive findings that were not of statistical significance (Bibbo et al, 1978;Clark and Portier, 1979;Hadjimichael et al, 1984;Colton et al, 1993); and another found no association (Greenberg et al, 1984).…”

mentioning

confidence: 99%

“…Of the studies assessing DES in relation to breast cancer mortality, one observed a significant association (Calle et al, 1996); four produced suggestive findings that were not of statistical significance (Bibbo et al, 1978;Clark and Portier, 1979;Hadjimichael et al, 1984;Colton et al, 1993); and another found no association (Greenberg et al, 1984). To date, only one study formally assessed all-cause or disease-specific mortality outcomes, and found little evidence of an association with DES (Greenberg et al, 1984).…”

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Mortality in women given diethylstilbestrol during pregnancy

et al. 2006

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We used Cox regression analyses to assess mortality outcomes in a combined cohort of 7675 women who received diethylstilbestrol (DES) through clinical trial participation or prenatal care. In the combined cohort, the RR for DES in relation to all-cause mortality was 1.06 (95% CI ¼ 0.98 -1.16), and 1.11 (95% CI ¼ 1.02 -1.21) after adjusting for covariates and omitting breast cancer deaths. The RR was 1.07 (95% CI ¼ 0.94 -1.23) for overall cancer mortality, and remained similar after adjusting for covariates and omitting breast cancer deaths. The RR was 1.27 (95% CI ¼ 0.96 -1.69) for DES and breast cancer, and 1.38 (95% CI ¼ 1.03 -1.85) after covariate adjustment. The RR was 1.82 in trial participants and 1.12 in the prenatal care cohort, but the DES -cohort interaction was not significant (P ¼ 0.15). Diethylstilbestrol did not increase mortality from gynaecologic cancers. In summary, diethylstilbestrol was associated with a slight but significant increase in all-cause mortality, but was not significantly associated with overall cancer or gynaecological cancer mortality. The association with breast cancer mortality was more evident in trial participants, who received high DES doses. British Journal of Cancer (2006) (Dieckmann et al, 1953;Swyer and Law, 1954), use continued for another two decades. Diethylstilbestrol was withdrawn from use during pregnancy in the early 1970s, after it was shown that in utero exposure was strongly associated with the risk of vaginal adenocarcinoma (Herbst et al, 1971). Until that time, as many as 2 million women in the US (Noller and Fish, 1974), and 4 million women worldwide (Newbold, 1993) were given DES during pregnancy.Most studies, but not all (Vessey et al, 1983), have suggested a positive association between DES taken during pregnancy and breast cancer incidence (Bibbo et al, 1978;Clark and Portier, 1979;Beral and Colwell, 1980;Greenberg et al, 1984;Hadjimichael et al, 1984;Colton et al, 1993;Titus-Ernstoff et al, 2001), although the latter four studies produced findings compatible with chance. Of the studies assessing DES in relation to breast cancer mortality, one observed a significant association (Calle et al, 1996); four produced suggestive findings that were not of statistical significance (Bibbo et al, 1978;Clark and Portier, 1979;Hadjimichael et al, 1984;Colton et al, 1993); and another found no association (Greenberg et al, 1984). To date, only one study formally assessed all-cause or disease-specific mortality outcomes, and found little evidence of an association with DES (Greenberg et al, 1984). In the present paper, we present findings based on the largest study to date of mortality outcomes in women with documented DES exposure. MATERIALS AND METHODSWe assessed exposure to DES during pregnancy in relation to cause-specific and total mortality, with a particular interest in gynaecological cancers, and those known to be influenced by exposure to exogenous oestrogen. The analyses were based on a combined cohort, the design and methods of which have been described pr...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Mortality in women given diethylstilbestrol during pregnancy

et al. 2006

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“…Subsequently, DES use was found to be associated with an increased risk of breast cancer in women who took the drug (Colton et al 1993). The latest results suggest that the DES daughters also have an increased risk of breast cancer after age 40 years (Palmer et al 2006).…”

Section: Examination Of the Supplementmentioning

confidence: 98%

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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Cancer Risk in Women Exposed to Diethylstilbestrol In Utero

Hatch

Palmer²,

Titus-Ernstoff³

et al. 1998

JAMA

174

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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.

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Breast Cancer in Mothers Prescribed Diethylstilbestrol in Pregnancy

Cited by 89 publications

References 18 publications

Mortality in women given diethylstilbestrol during pregnancy

Mortality in women given diethylstilbestrol during pregnancy

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

Cancer Risk in Women Exposed to Diethylstilbestrol In Utero

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