DES daughters at higher risk

DES, an anti-miscarriage drug prescribed to millions of pregnant women from the 1940s to the early 1970s, has an unfortunate legacy for the daughters of these women: nearly double the average risk of developing breast cancer, according to a recent study by the BU School of Public Health.

The study, published in the medical journal Cancer Epidemiology, Biomarkers, and Prevention, recruited 4,817 women over 40 whose mothers were prescribed DES, along with 2,073 women of the same age whose mothers did not take the drug. Researchers found that the women exposed to DES (diethylstilbestrol), a synthetic form of estrogen, had a 91 percent higher risk of developing the disease after age 40 and a threefold increased risk after age 50 compared to women who never came in contact with the drug.

The so-called “DES daughters” were already known to have a greater risk of clear cell carcinoma of the vagina and the cervix as well as pregnancy complications and infertility. “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,” says lead author Julie Palmer, an SPH professor of epidemiology.

The authors urge women exposed to DES in the womb not only to have regular screening for gynecologic cancers, but also to have annual mammograms. Palmer says she hopes the study “increases awareness for exposed women and physicians of the importance of the pap smear, the pelvic exam, and the breast exam. It’s more important for DES daughters to do these things than for the average woman.” Women exposed to DES should also be careful about using supplemental female hormones, which boost estrogen levels. Use of these hormones is in itself an independent breast cancer risk factor, according to the study authors. “Their use could compound an already increased risk,” says Palmer.

As many as five million American women took DES, affecting about 2.4 million of their daughters. Studies on the 2.4 million “DES sons” are ongoing — they may be at greater risk for developing testicular cancer and other genital abnormalities, but findings so far have been inconsistent.

Some scientists say the reason DES daughters are at increased risk for breast cancer may be because the estrogen in the drug increases the number of breast tissue stem cells available at birth — cells that could transform into cancer. “We don’t actually know how it works,” says Palmer. “That’s one theory put forth by some epidemiologists who have been focusing on prenatal factors of breast cancer. We plan to do some more research to try to elucidate that theory now that we see the overall association.”

Palmer says that she and her colleagues also plan to examine whether DES daughters have an increased risk of such hormone-dependent cancers as ovarian and endometrial cancer.

DES was developed in 1938 for women believed to have an increased risk of miscarriages and premature births. The drug was even touted as helping mothers produce bigger, healthier babies and reducing pregnancy-related high blood pressure and morning sickness. In 1953, however, a clinical study found that DES did nothing to affect miscarriage risk. Nonetheless, it wasn’t removed from the market until 1975, after the increased risk of cancers of the vagina and the cervix for DES daughters became known. The latest BU study is the first direct evidence that prenatal exposure to excess estrogen may have an effect on developing breast cancer.

And although the study suggests that as DES daughters get older, they have a higher risk of breast cancer, according to the authors, it is not definite that they will develop the disease. “This risk is about the same as having a first-degree relative with breast cancer,” Palmer says, adding that regular physical activity is believed to help reduce the risk. “Probably the most definitive of all factors for postmenopausal women is for them to keep their weight down,” she says. “Women who are past menopause and overweight have perhaps a 30 percent increased risk of breast cancer compared to those who aren’t overweight.”