Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

Women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later. The finding, from the Million Women Study (MWS)—a large observational study in the United Kingdom—adds to a growing body of evidence that the use of combined hormone therapy (estrogen plus progestin) to treat menopausal symptoms increases the risk of breast cancer and deaths from the disease. The results appeared in the Journal of the National Cancer Institute on January 28.

The pattern of increased breast cancer risk “was seen across different types of hormonal therapy, among women [in the MWS] who used hormonal therapy for either short or long durations, and also in lean and in overweight and obese women,” Dr. Valerie Beral of Oxford University and her colleagues wrote. Their findings support results from the Women’s Health Initiative (WHI), a randomized clinical trial that, in 2002, first reported evidence linking combined hormone use to breast cancer.

“The new findings underscore the idea that there’s really no safe window of time for women to take combined hormone therapy,” said Dr. Leslie Ford of NCI’s Division of Cancer Prevention and the Institute’s WHI liaison. After the initial WHI results were announced, she noted, some people had argued that hormones may be safer when started at the time of menopause. “The new findings refute that argument,” she added.

WHI and MWS investigators have both reported that breast cancer incidence rates declined rapidly once women stopped taking combined hormone therapy. “It is important for women to know that if they stop using hormones, the risk of breast cancer very quickly returns to where it was before hormone therapy began,” Dr. Ford said.

There has been a discrepancy between the WHI and MSW results to date as to whether estrogen-only therapy raises breast cancer risk in postmenopausal women. WHI reports have found little risk associated with this treatment, whereas the MWS investigators have observed a statistically significant increased risk.

Additional follow-up from the WHI estrogen-only intervention trial should help clarify this issue in the coming years, noted Drs. Rowan T. Chlebowski of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Garnet L. Anderson of the Fred Hutchinson Cancer Research Center in an accompanying editorial.