Early Oral Contraceptive Formulations Linked To Breast Cancer Risk

"If there is a risk associated with current formulations, we probably don't have the data to detect it," says Thomas Sellers, Ph.D., Mayo Clinic Cancer Center epidemiologist and senior investigator of this study. "What our data suggest is that it is early formulations with high doses of estrogen and progestins that pose a risk, not later ones. More importantly, these results don't apply for women at average risk for breast cancer, who should not interpret the study as reason to change their contraceptive practices."

The study, to be published in the Oct. 11, 2000, issue of Journal of the American Medical Association, found that the risk of breast cancer is 3.3 times greater for breast cancer patients' sisters and daughters who had ever used oral contraceptives compared to those with similar risk who had never used oral contraceptives. This did not apply to nieces, granddaughters or women who married into the family, who only had a 1.2-fold greater risk of breast cancer with pill usage. In families in which five or more blood relatives had been diagnosed with breast or ovarian cancer, the risk was even greater. In those families, sisters and daughters of the breast cancer patients were 11.4 times more likely to develop breast cancer if they had ever taken oral contraceptives.

The elevated risk for first-degree relatives (sisters, daughters) of breast cancer patients was particularly evident for women who had used oral contraceptives introduced prior to 1975, when the formulations were more likely to contain higher doses of estrogen and progestins. The study could not make statistically significant conclusions about sisters and daughters of breast cancer patients who had used more recent formulations of oral contraceptives containing lower doses of estrogen and progestins, due to the small number of women in the study who had taken them.

This is the first family, or multigenerational, study of the association between oral contraceptive use and the development of breast cancer in women with a family history of the disease. It included 426 families of women diagnosed with breast cancer between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Participants included 394 sisters and daughters of the breast cancer patients, 3,002 granddaughters and nieces, and 2,754 women who married into the families. Follow-up data were collected via phone interviews with these participants between 1991 and 1996.

"We knew that oral contraceptive use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to the disease was less clear," says Dr. Sellers. "This new study gives us more information for that population."

Oral contraceptive use by women with a family history of breast cancer is an issue due to the ongoing controversy regarding its risks and benefits.

"This study provides information that must be considered in light of the recommendations that have been made for women at high genetic risk for breast or ovarian cancer to use oral contraceptives to reduce the risk of ovarian cancer," says Dr. Sellers. "Although there is a good body of scientific evidence that use of oral contraceptives does lower risk of ovarian cancer, we need to be sure that this doesn't come at the expense of an increased risk for breast cancer."

The study's authors do not recommend additional screening for women who have taken earlier formulations of oral contraceptives and also have first-degree relatives with breast cancer, but they encourage these women to be sure to follow the recommended screening guidelines.

"Prevention of breast cancer is our goal," says Dr. Sellers. "When that isn't possible, then early detection is essential. Women at high familial risk who've been exposed to oral contraceptives with high doses of estrogens and progestins should be particularly vigilant regarding mammography."