HRT and Tender Breasts May Indicate Increased Breast Cancer Risk

< Oct. 14, 2009 > -- Women taking estrogen/progestin hormone replacement therapy who experience breast tenderness may be at increased risk for developing breast cancer, according to a new study released this week.

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.

However, before recommending that women taking these hormones who experience sore breasts stop taking the medications, the researchers say more study is needed. But women who develop breast tenderness might want to reassess if the hormones are really necessary to control their menopausal symptoms.

The study is published in the Archives of Internal Medicine.

"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," says 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 says.

WHI Data Used

Dr. Crandall's team used data from the Women's Health Initiative (WHI), 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, Dr. Crandall says. 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 (inactive substance). 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.

More Clues Sought

Researchers are not certain why some women on hormone therapy develop breast cancer while others do not, though the breast tenderness may provide a clue, Dr. Crandall says. Tenderness could be a sign that the cells of the breast are multiplying rapidly. Rapid cell growth is a risk factor for cancer.

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

However, why this happens to some women and not to others is still not well understood, Dr. Daly says.

"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," she says. "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."

Study participants took daily doses of oral conjugated equine estrogens (0.625 milligrams) plus medroxyprogesterone acetate (2.5 milligrams).

Dr. Crandall says the findings apply only to women taking the combination hormone therapy, not women who have had hysterectomies and are taking estrogen alone.

Wyeth Pharmaceuticals, which makes the estrogen-progestin therapy Prempro, issued a statement calling 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."

Always consult your physician for more information.

More About Hormone Replacement Therapy

To learn more about women's health, and specifically hormone replacement therapy, the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) launched the Women's Health Initiative (WHI) in 1991. The hormone trial had two studies: the estrogen-plus-progestin (HRT) study of women with a uterus and the estrogen-alone (ERT) study of women without a uterus. Both studies were concluded early when the research showed that hormone replacement did not help prevent heart disease and it increased risk for some medical problems.

The WHI recommends that women follow the Food and Drug Administration (FDA) advice on hormone (estrogen-alone or estrogen-plus-progestin) therapy. It states that hormone therapy should not be taken to prevent heart disease.

These products are approved therapies for relief from moderate to severe hot flashes and symptoms of vulvar and vaginal atrophy. Although hormone therapy is effective for the prevention of postmenopausal osteoporosis, it should only be considered for women at significant risk of osteoporosis who cannot take non-estrogen medications.

The FDA recommends that hormone therapy be used at the lowest doses for the shortest duration needed to achieve treatment goals.

Postmenopausal women who use or are considering using hormone therapy should discuss the possible benefits and risks to them with their physicians.

The National Heart, Lung, and Blood Institute offers the following suggestions for women who are deciding whether or not to use postmenopausal hormone therapy:

• Because the study involved healthy women, only a small number of them had either a negative or positive effect from estrogen plus progestin therapy. The percentages describe what would happen to a whole population - not to an individual woman. In the estrogen plus progestin therapy study the increased risk of breast cancer was less than a tenth of 1 percent each year. When this risk is applied to a large group of women and over several years, then the number of women affected becomes a public health concern.
• The most important thing a woman can do in deciding to continue hormone replacement therapy is discuss the current research with her physician and healthcare team.
• Women need to be aware that taking a combined progesterone and estrogen regimen or estrogen alone is no longer recommended to prevent heart disease. A woman should discuss other alternatives of protecting the heart with her physician.
• Women should discuss with their physicians the value of taking combined progesterone and estrogen replacement therapy or estrogen to prevent osteoporosis. There may be alternative treatments based on a woman's unique health profile.

Always consult your physician for more information.