April 11, 2006 -- After hysterectomy, estrogen-only hormone therapy does not increase a woman's risk of breast cancer.

That's the word from the final analysis of the estrogen-only arm of the Women's Health Initiative (WHI) study. The trial was stopped early because it linked hormone therapy to increased risk of stroke, with no reduction in heart-disease risk.

The study had two arms. Menopausal women with an intact uterus received estrogen plus progestin or an inactive placebo. That's because estrogen alone increases a woman's risk of uterine cancer. Women who had undergone hysterectomy, however, received estrogen-only hormone therapy or placebo.

The average five-year breast cancer risk estimates were similar between the estrogen-plus-progestin group and the estrogen-only group.

Could this be true? Stanford researcher Marcia L. Stefanick, PhD, chairwoman of the WHI steering committee, led a team that took a detailed look at the estrogen-only data. Stefanick's report appears in the April 12 issue of The Journal of the American Medical Association.

"The major finding is no increased risk of breast cancer in women taking just estrogen," Stefanick tells WebMD. "There is a tendency for decreased risk of breast cancer, but it is not statistically significant. This means it would be inappropriate simply to say estrogen alone decreases breast cancer."

Stefanick says estrogen may be safer for some women than for others.

"Women at lower initial risk of breast cancer seem to be the ones who have even lower risk if they go on estrogen," she says. "Women with a higher risk of breast cancer seem to have even higher risk with estrogen."

HRT Risk Overblown?

Stefanick says there are big differences between treating women who have had a hysterectomy and women with an intact uterus. And there are big differences between estrogen-only hormone therapy and estrogen-plus-progestin therapy.

"The media always talk about 'hormones do this' or 'hormones do that,'" Stefanick says. "What we are clear on is estrogen plus progestin does one thing in one group, and estrogen alone does something very different in a different group. We cannot say it is all about progestin. But we can say progestin plus estrogen gives a really different outcome than just estrogen."

The study results are very reassuring to Hugh Taylor, MD, associate chief for research in the obstetrics, gynecology, and reproductive sciences department at Yale University. Taylor spoke at a news conference organized by Wyeth, which makes Premarin and Prempro, the hormones tested in the WHI study. Taylor has received speakers' fees from Wyeth, but has no financial interest in the company. Wyeth is a WebMD sponsor.

Controversy Continues

"Women have been on a roller coaster ride. That ride is over," Taylor says. "For women with hysterectomy, the evidence is clear: Estrogen is safe for them. There is no breast cancer risk for estrogen alone. This has been the No. 1 fear keeping women from using estrogen for their menopausal symptoms."

While the study did not consistently find an overall reduction in breast cancer, the women on estrogen-only therapy did have significantly fewer cases of the most common kind of breast cancer -- ductal cancer.

"What was significantly decreased was ductal cancer, the most common form, a real reduction by almost 30% in the most common kind of breast cancer," Taylor says.

What about women who have not had a hysterectomy?

"As we see more detailed results from the WHI, we see there are some reassuring findings for women without hysterectomy," Taylor says. "In terms of heart disease, in younger women there is no increased risk. Ongoing studies with newly menopausal women are suggesting a benefit even with combined estrogen/progestin treatment. There was increased risk of breast cancer, but this number was very small. On balance, the risks of estrogen plus progestin are very low."

That's a controversial opinion. Boston University epidemiologist Lynn Rosenberg, ScD, recently analyzed data from a study of more than 23,000 black women. Reporting in the April 10 issue of the Archives of Internal Medicine, she finds that women who used hormone therapy -- even estrogen alone -- had a higher risk of breast cancer than women who never used hormone therapy.

"In my view, the weight of evidence would make me very suspicious of estrogen alone," Rosenberg tells WebMD. "It seems absolutely certain that estrogen plus progestin increases the risk of breast cancer, particularly if you take if for a long time."

Doctors currently prescribe hormone therapy for women who need help with the symptoms of menopause. Taylor says every woman with these symptoms is a candidate for this treatment, unless they have a high risk of breast cancer or a clotting disorder.

"The paradigm of treating menopause symptoms with the lowest effective dose of hormone therapy, for the shortest period necessary, is very sensible," Taylor says.

SOURCES: Stefanick, M.L. The Journal of the American Medical Association, April 12, 2006; vol 295: pp 1647-1657. Marcia L. Stefanick, PhD, professor of medicine, Stanford University School of Medicine; chairwoman, Women's Health Initiative steering committee. Wyeth news conference with Hugh Taylor, MD, associate professor and associate chief for research, department of obstetrics, gynecology & reproductive sciences, Yale University; and William T. Creasman, MD, professor of obstetrics and gynecology, Medical University of South Carolina. Lynn Rosenberg, ScD, professor epidemiology, Boston University.

Reviewed by Louise Chang