DES Daughters at Higher Risk of Breast Cancer

BOSTON, Aug. 7 -- Women whose mothers took the synthetic estrogen DES (diethylstilbestrol) have a sharply increased risk of breast cancer once they are 40 or older, according to researchers here.

"This is really unwelcome news because so many women worldwide were prenatally exposed to DES, and these women are just now approaching the age at which breast cancer becomes more common," said Julie Palmer, Sc.D., of the Boston University School of Public Health here.

The so-called DES daughters -- perhaps as many as two million in the U.S. -- were already known to be at higher risk of clear cell carcinoma of the vagina and cervix and their mothers have already been shown to be at higher risk of breast cancer.

But the current study, published in the August issue of the journal Cancer Epidemiology, Biomarkers & Prevention, is the first to show clearly that the DES daughters are at higher risk of breast cancer as they age than are women who weren't exposed to the drug, Dr. Palmer and colleagues said.

On a basic science note, the finding is support for the hypothesis that one risk factor for breast cancer is prenatal exposure to higher than normal levels of estrogen, Dr. Palmer said. "That theory has been around, but it has been difficult to study," she said. "The DES tragedy offers us a direct way to test the hypothesis."

The finding comes from a long-term cohort study with follow-up that began in many cases in 1978. An earlier analysis of the cohort did not show an increased breast cancer risk, Dr. Palmer and colleagues said, but at the time most of the women were relatively young.

Indeed, for this study, the age-adjusted incidence rate ratio, comparing 4,817 DES daughters and 2,073 unexposed women, was greater for the exposed women, but not significantly so over the whole cohort.

However, Dr. Palmer and colleagues found, DES daughters 40 or older had nearly twice the risk of incident breast cancer than women in the unexposed cohort. The incidence rate ratio was 1.91, with a 95% confidence interval from 1.09 to 3.33, which was statistically significant at P=0.03.

The rate ratio was even higher for women 50 and older, the researchers said, but the numbers of women in that age bracket were too few to make a precise estimate of risk.

The association did not differ by receptor status of the tumor, tumor size, or lymph-node involvement. Furthermore, the highest relative risk was observed for the cohorts receiving the highest cumulative dose of DES exposure.

Over the whole cohort, there were 102 cases of incident breast cancer -- 76 among the DES daughters (with 98,591 person years of follow-up) and 26 among the unexposed women (with 35,046 person-years of follow-up).

Clinically, the finding suggested that DES daughters and their physicians should be vigilant about breast cancer screening, including regular mammograms, and be careful about using supplemental hormones.

The study found no statistical interaction between prenatal DES exposure and the use of hormone supplements, but the study had limited power to detect an interaction. "Because the commonly used female hormone supplements have been shown to independently increase risk of breast cancer, it might be wise for exposed women to avoid such supplements whenever possible."

"Use of hormone supplements is, in itself, an independent breast cancer risk factor," Dr. Palmer said, "and women may choose not to compound their already increased risk."