Women who take hormone therapy that includes estrogen and progestin are at increased risk of developing breast cancer and dying from it, especially if they start taking the therapy just as menopause begins, a new analysis confirms.
Researchers followed nearly 42,000 women, all of whom were past menopause, for an average of more than 11 years. Of those, more than 25,000 did not use hormone therapy and more than 16,000 took estrogen and progestin, also called combined hormone therapy. For this analysis, the researchers did not include estrogen-only therapy, used by women who have had a hysterectomy.
At the end of the follow-up period, more than 2,200 of the women were found to have breast cancer. Compared to non-users, those who took combined therapy were more likely to have breast cancer, said Dr. Rowan Chlebowski, a medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. Chlebowski led the study, which was published in the March 29 issue of the Journal of the National Cancer Institute.
The link has been found in other studies, but Chlebowski also found the risk was greatest among those who took the hormones closest to menopause. "Women starting within months of menopause had about a threefold greater risk than women starting 10 years after menopause," Chlebowski said.
For the new analysis, Chlebowksi looked at results from the Women's Health Initiative observational study. He compared the findings with those from the Women's Health Initiative randomized clinical trial, in which women were assigned to different treatments.
The Women's Health Initiative included four clinical trials and an observational study. Women were all past menopause and were aged 50 to 79.
Chlebowski said he did the new analysis to resolve what he saw as unanswered questions. In the trial, only about one-third, or 5,000, of the women were in their 50s when they started the study. As that is the typical age for menopause to start, about two-thirds of the women in the trial were in their 60s or beyond, so began to take hormones several years after menopause.
Chlebowski set out to see if the link between breast cancer risk and combined hormone therapy use was influenced by earlier use of hormones.
"We had a substantial number closer to menopause than the clinical trial of [the Women's Health Initiative]," he said.
He found, however, that not only was the risk of breast cancer still increased, but it also increased even more if the women were closer to menopause when they began to take the hormones.
He speculated that women who start the hormone therapy close to menopause still have circulating levels of estrogen high enough to make them exceed some threshold, beyond which it may become hazardous.
Progestin is thought to play a role, too, he added.
Although others have thought that the breast cancers linked with combined hormone therapy are often ones with a somewhat better outlook -- another question Chlebowski thought needed more study -- he did not find that in his new analysis.
The new analysis reinforces the finding that combination hormone therapy is linked with higher breast cancer risk, said Dr. Joanne Mortimer, director of Women's Cancer Programs at the City of Hope Comprehensive Cancer Center in Duarte, Calif.
Although previous research has found some good effects of hormone therapy on the heart, she and Chlebowski said that has to be weighed against the breast cancer risk found in much other research.
The new analysis also suggests that "the time of starting hormone therapy really matters," Mortimer said. Although the analysis found an association between the two, it did not prove a cause-and-effect link.
Mortimer and Chlebowski agreed that women need to discuss the pros and cons of hormone therapy during menopause with their doctors.
Women should seriously consider whether their symptoms, such as hot flashes and night sweats, are limiting enough to warrant taking hormones, Chlebowski said. Although some women are severely bothered by symptoms, he said, others may be less bothered and can avoid hormone therapy.