In the nearly 11 years since researchers first rang alarm bells that women on hormone replacement therapy faced an increased risk of breast cancer, some have suggested that taking estrogen and progestin to treat symptoms of menopause might not be so dangerous after all.
Though it was generally agreed that woman who took the two hormones to curb their hot flashes and night sweats upped their chances of developing the disease, many studies suggested that the cancers the women developed were less likely to be deadly.
A new analysis of data from the Women's Health Initiative now casts doubt on those findings. The study, published Friday by the Journal of the National Cancer Institute, concludes that the prognosis for cancers related to hormone replacement therapy is just as dire as for other breast cancers. As a result, women who turn to the treatment are more likely to die of breast cancer than their peers who don't take hormones.
"You could fill a basketball arena with the women who get the disease," said Dr. Rowan Chlebowski, the principal investigator for the Women's Health Initiative and lead author of the new study. "It seems like you'd want to reach a higher threshold before you take it."
Nearly 70,000 postmenopausal women participated in randomized clinical trials as part of the Women's Health Initiative project. The study participants who took estrogen plus progestin had higher rates of breast cancer diagnoses and of breast cancer deaths.
At the same time, more than 90,000 additional women took part in a related observational study that tracked details about their health and hormone use over an average of 11 years. Along with many other observational studies, this one found that women who took hormones to treat menopause symptoms and got breast cancer were less likely to die from the illness than women who got breast cancer without taking hormones.
Chlebowski, an oncologist based at the Los Angeles Biomedical Research Institute in Torrance, suspected that the discrepancy could have resulted from key differences between the women in the randomized trial and the women in the observational study.
So he and his team identified a subset of more than 41,000 women from the observational study who more closely matched the women who took part in the randomized trial. In doing so, the researchers set aside data on women who were not using hormones when they participated in a study but had taken them in the past — a factor that had the potential to complicate the findings.
The new results fell more closely in line with the findings from the original randomized trial: Survival after breast cancer was similar for both hormone users and non-users. Tumors that arose in women who took hormones were no less deadly.
They had appeared to be, however, because women who had taken hormones years before might have already developed aggressive cancers and would not have been able to participate in the study in the first place. Because of the study design, they had been selected out, Chlebowski said.
Dr. Patricia Ganz, director of cancer prevention and control research at UCLA's Jonsson Comprehensive Cancer Center, applauded the new study's rigor.
"If you're going to take these therapies, you need to know there's an increased risk," said Ganz, who was not involved in the study. "Make sure there's a good indication. And don't take them for a long period of time."
The new findings apply only to women who take estrogen and progestin, a synthesized form of the natural hormone progesterone. Women who have had hysterectomies can take estrogen alone, a regimen that doesn't seem to increase breast cancer risk. But those who still have a uterus must take both estrogen and progestin to avoid developing endometrial cancer.
When the Women's Health Initiative was launched in 1993, about 40% of postmenopausal women were taking hormones. Many of them — and their doctors — believed they'd get benefits including improved bone, cardiovascular and cognitive health, Chlebowski said.
As research revealed that was not the case, and that the treatment was associated with cancer risk, the number of users fell by half, to about where it remains today.
Dr. Joanne Mortimer, director of the Women's Cancers Program at City of Hope Cancer Center in Duarte, said that in general, she does not recommend hormone replacement therapy for patients with menopause symptoms.
But Mortimer, who was not involved with the study, said she does discuss the pros and cons of the treatment with "the ones who are up all night with hot flashes and want to kill people. There are still women on it and they will cut your arm off if you take it away."
For a certain percentage of women, she added, hormones provide the only relief.
Last year, a coalition of women's health groups led by the North American Menopause Society, the American Society for Reproductive Medicine and the Endocrine Society issued a statement reiterating that hormone therapy was "still an acceptable treatment for menopausal symptoms." They called the treatment "relatively safe."