Progestin adds to breast cancer risk

Hormone-replacement therapy for women during and after menopause can maintain bone strength, ease menopausal symptoms, and perhaps fend off heart disease. Two new studies indicate, however, that women whose therapy combines two common hormones, estrogen and progestin, are more likely to get breast cancer than women who receive estrogen alone.

Physicians routinely add progestin to estrogen prescriptions because it seems to limit the risk of uterine cancer. Some women take it daily, some for only part of the month.

A group led by researchers at the National Cancer Institute (NCI) in Rockville, Md., tracked 2,082 cases of breast cancer among 46,355 postmenopausal women across the United States.

The team found that the first years of combined hormone therapy each impart an 8 percent increase in risk of breast cancer per year of use, compared with a 1 percent increase associated with estrogen alone. Thus, 3 years of using the combination would yield a 24 percent greater risk, while estrogen alone would boost it by only 3 percent, the researchers report in the Jan. 26 Journal of the American Medical Association.

Beyond that period, the risks become unclear since the study subjects’ average time on combined therapy was only 3.6 years. “It’s safer not to extrapolate too far,” says study coauthor Catherine Schairer, an epidemiologist at NCI.

The increase in risk seems to be short-lived, she says. Women who had quit the combined therapy at least 4 years before the study had no greater breast cancer risk than women who had never taken it.

In the other study, Ronald K. Ross and his colleagues at the University of Southern California in Los Angeles compared 1,897 breast cancer patients with 1,637 women of similar average age without cancer. The researchers interviewed each woman during or after menopause, between ages 55 and 72.

Women in this study who had received combined estrogen-progestin therapy for 5 to 10 years were 51 percent more likely than average to have been diagnosed with breast cancer, while those on estrogen alone faced a slightly decreased risk, the researchers report in the Feb. 16 Journal of the National Cancer Institute.

Progestin, which seems to repress estrogen receptors in the uterus’ inner lining, may activate these receptors in the breast and spur cell growth, Schairer says.

In a commentary accompanying Schairer’s report, three researchers of the Harvard School of Public Health in Boston suggest that women who have had their uterus removed shouldn’t take progestin. Meanwhile, women with an intact uterus must carefully weigh the benefits and risks—now better defined—of combined therapy, say Walter C. Willett, Graham A. Colditz, and Meir J. Stampfer.