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Combined Hormone Therapy Makes Breasts Denser

It may be harder to detect tumors, clinicians say

FRIDAY, Jan. 3, 2003 (HealthDayNews) -- Women on combination hormone therapy may have denser breast tissue, researchers report.

While women taking a combination of estrogen and progestin seem to have 3 percent to 5 percent denser tissue than women taking estrogen alone or placebo, this does not necessarily translate into a greater risk for breast cancer, cautioned lead researcher Dr. Gail Greendale, a professor of medicine at the University of California Los Angeles School of Medicine.

"There are no data that prove that an increase in mammographic density equates to an increase in breast cancer risk," she said.

While some studies have suggested such a link, they were observational studies, and more research needs to be done to prove an association between dense tissue and breast cancer -- particularly dense tissue that results from hormone therapy, she said.

The new research, appearing in the current issue of the Journal of the National Cancer Institute, is not the first to find a connection between combination therapy and denser breast tissue, Greendale said. Her own study group published a paper suggesting a link in 1999, but more accurate ways to measure mammographic density have been developed since. Using these better measures, the researchers were able to confirm those earlier findings, she said.

"In our prior research, we showed that estrogen only did not produce a statistically significant increase in mammographic density, while each of the three estrogen-plus-progestin regimens did so," Greendale said. "However, the method of measuring mammographic density that we used in our 1999 study was much coarser than the method we used in the new study." Furthermore, the first study did not look at the magnitude of the increase in breast density, the researchers note.

For the new study, the researchers obtained baseline and 12-month mammograms of 571 women, aged 45 to 64, enrolled in the Postmenopausal Estrogen/Progestin Interventions Trial. The women were randomized to receive placebo, estrogen only, or one of three combinations of estrogen and progestin. The researchers then analyzed digitized mammograms to determine the percentage of the left breast that was composed of dense tissue. Linear regression analysis was used to determine the effects of treatment on change in mammographic density.

Greater mammographic density was found to be associated with the use of estrogen/progestin therapy, but not with the use of estrogen alone. There was little difference between the women on estrogen alone and those taking placebo.

In an accompanying editorial, Dr. Rowan Chlebowski of the Harbor-UCLA Research and Education Institute in Torrance, Calif., and Dr. Anne McTiernan of the Fred Hutchinson Cancer Research Center in Seattle, note that the effects of the hormone preparations, when they were connected with denser tissue, were relatively small.

"The authors themselves raise the most critical question -- what is the link between such changes in breast density in women receiving postmenopausal hormone therapy and subsequent changes in breast cancer risk?" they write.

Dr. Carolyn Runowicz, director of Gynecologic Oncology Research at St. Luke's-Roosevelt Hospital Center in New York City, agreed that while this study is well-done, it doesn't answer the main, pressing question. "They have not linked a change in breast density with a change in risk of breast cancer."

The important message that this study conveys is that "clinicians and patients need to understand that the mammograms on women on HRT may be more difficult to interpret, due to the change in density. Thus, a palpable mass and a negative mammo[gram] need to be immediately investigated," she said.

Women with dense breasts receiving a mammogram may need other tests such as breast sonograms or magnetic resonance imaging to rule out tumors, Runowicz said, although more studies are also needed to assess these other tests.

Greendale's group next plans to study whether the degree of change in hormone levels that result from taking combination hormonal therapy is related to the amount of change in mammographic density.

What To Do

To find out more about the importance of breast density, visit the Radiological Society of North America. Meanwhile, the National Women's Health Information Center has updated information on hormone replacement therapy.

SOURCES: Gail Greendale, M.D., associate professor of medicine and geriatrics, David Geffen School of Medicine, University of California, Los Angeles; Carolyn Runowicz, M.D., director of gynecologic oncology research, St. Luke's-Roosevelt Hospital Center, New York; Jan. 1, 2003 Journal of the National Cancer Institute
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