With Hormone Therapy, Tender Breasts May Signal Cancer Risk

By Jennifer Thomas
HealthDay Reporter

MONDAY, Oct. 12 (HealthDay News) -- Breast tenderness in women taking estrogen/progestin hormone replacement therapy could signal increased chances of developing breast cancer, a new study says.

Women taking estrogen plus progestin who reported developing breast tenderness after starting the hormone therapy were 48 percent more likely to develop invasive breast cancer than women on hormone therapy who did not experience breast tenderness.

Researchers said more study is needed before they would recommend that women who experience this symptom discontinue taking the hormones. But women who develop breast tenderness might want to reassess if the hormones are really necessary to control their menopausal symptoms.

"It's too soon to tell women to quit their hormone therapy, but it is something for women to think about in balancing the risks versus the benefits," said the study's lead author, Dr. Carolyn J. Crandall, a clinical professor of general internal medicine and health services research at the David Geffen School of Medicine at the University of California, Los Angeles.

"Breast tenderness is a symptom that may be a risk marker for breast cancer," she said.

The study is in the Oct. 12 issue of the Archives of Internal Medicine.

Researchers used data from the Women's Health Initiative, a landmark federal study that was halted in 2002 after investigators determined that hormone replacement therapy increased the risk for heart attack, stroke and invasive breast cancer.

Since then, most women have been advised to use hormone replacement therapy -- which physicians now call menopausal hormone therapy -- either not at all or for the shortest duration possible to get them through their most uncomfortable menopausal symptoms, usually hot flashes, Crandall said. Women are strongly advised to avoid taking hormones for longer than five years, when the risk for breast cancer doubles.

In the new study, more than 8,500 women took estrogen plus progestin, and more than 8,100 took a placebo. Participants were given a mammogram and breast exam at the start of the trial and annually thereafter.

At the one-year mark, women on the combination therapy were three times more likely to report experiencing breast tenderness than women on the placebo. About 36 percent of women on the hormone therapy reported new breast tenderness, compared with nearly 12 percent of women on a placebo.

During 5.6 years of follow-up, 0.6 percent of women who reported new breast tenderness were diagnosed with breast cancer each year, compared with 0.36 percent of women taking hormones who did not experience new breast tenderness.

Researchers aren't certain why some women on hormone therapy develop breast cancer while others don't, though the breast tenderness may provide a clue, Crandall said. Tenderness could be a sign that the cells of the breast are multiplying rapidly. Cell proliferation is a risk factor for cancer.

Mary B. Daly, director of the Personalized Cancer Risk Assessment Program at Fox Chase Cancer Center in Philadelphia, said the findings of the study, which she described as well done, should prompt women and their doctors to reassess the need for hormone replacement if such tenderness develops.

Yet individual differences -- why this happens to some women and not others -- are still not well understood, Daly said.

"Some women who start taking hormone therapy may have cells that are much more receptive to it, or more sensitive to it, while other women must be more resistant," Daly said. "Something must be different about the breast tissue to make it more or less responsive to the hormones. If we could figure that out, that would be great."

Women in the study were taking daily doses of oral conjugated equine estrogens (0.625 milligrams) plus medroxyprogesterone acetate (2.5 milligrams).

The findings apply only to women taking the combination therapy, not women who've had hysterectomies and are taking estrogen alone, Crandall said.

In a statement, Wyeth Pharmaceuticals, which makes the estrogen-progestin therapy Prempro, called the study "interesting" but added that, "breast tenderness is not an established risk factor for breast cancer." According to the company, up to a quarter of women who take combination hormone therapy will develop some tenderness in the breast, typically transient. The company also noted that the "small" increase in breast cancer risk for women on combo therapy and those on placebo, "has previously been reported and is included in the Prescribing Information (labeling) for Prempro."