Taking the drugs around the time of menopause carries significantly more risk for the disease than starting them later, after a gap of at least five years, the study found. And while the study confirms that breast cancer risk rises with increasing time on the drugs, even women who took them for less than five years had more breast cancers than nonusers.
The analysis, published Jan. 28 in the Journal of the National Cancer Institute, looked at data from the Million Women Study, which recruited a quarter of all British women ages 50 to 64 in the late 1990s through 2001. Though not a clinical trial in which participants are randomly assigned to either a treatment or control group — considered the most telling and bias-free approach — the size of this study makes it a key addition to the Women's Health Initiative. In that large U.S. trial, the study of estrogen-progestin HRT was halted in 2002 because of evidence that the treatment, while reducing colon cancer and hip fractures, promoted heart disease, stroke and blood clots — as well as breast cancer.
Millions of women still take hormones
Since then, millions of women have stopped taking hormones, and many physicians have stopped recommending long-term hormone therapy for prevention of cardiovascular disease and osteoporosis, a common practice in the 1990s. But millions of American women continue taking hormone replacement to relieve hot flashes, vaginal dryness and other menopausal symptoms. Clinical guidelines generally advise taking hormones at the lowest dose and for the shortest time possible — typically around the time menopause begins — when symptoms strike.
Assessing the risk
Most women's absolute chance of getting breast cancer is small. In the British study, the incidence of breast cancer among women in their 50s who never used hormone therapy was 0.30 percent, doubling to 0.61 percent in women who took an estrogen-progestin combination before or within five years of menopause.
Also reassuring is the finding, affirming earlier studies, that when hormone users stopped taking the drugs, their risk fell to that of nonusers within a few years.
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Still, the findings are likely to revive questions about just how to balance the risks and benefits of estrogen-progestin therapy in early menopause. Partly because cardiovascular risks seem to accrue only in older women on HRT, some experts have suggested that women seeking relief from symptoms in their 50s can take the drugs for up to five years without concern. But often the general advice to limit time on medications hasn't been translated into any specific guidance on when to consider going off HRT, says Rowan T. Chlebowski, M.D., a cancer specialist at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and lead investigator of the Women's Health Initiative, who coauthored an editorial accompanying the British study. "Few doctors are saying, 'After a year or two years, let's stop and see if the symptoms return and you still need the treatment.' I think people will just tend to stay on it," he says.
Increased risk of death from breast cancer
Chlebowski and his coauthors published an analysis of Women's Health Initiative data in the Oct. 20 Journal of the American Medical Association addressing another long-standing question about HRT: whether breast cancers associated with the therapy tend to be relatively nonaggressive and treatable.
In fact, the study found, the therapy seemed to raise a woman's likelihood of dying from breast cancer, an outcome also observed among women in the Million Women Study.
"Estrogen plus progesterone increases the frequency of death from lung cancer [a finding published in 2009] and breast cancer, the two most common causes of cancer death in women," says Chlebowski. "That really sounds like something you want to be hesitant about taking."
Katharine Greider lives in New York and writes about health issues.