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Drop in Breast Cancer Rates Due to Drop in HRT Use

Researchers say first two years of combined hormone therapy a 'safe' period

WEDNESDAY, Feb. 4 (HealthDay News) -- A new analysis shows that the drop in breast cancer cases that began in 2003 is indeed due to women stopping hormone replacement therapy (HRT) after a large, U.S. study showed surprisingly higher rates of heart problems and breast cancer among users of some kinds of HRT.

Some experts have suggested such a theory explains the trend, while others have said it might be related to changes in mammography use.

"If you stop hormones, the risk of breast cancer [associated with hormone use] rapidly declines," said Dr. Rowan Chlebowski, a medical oncologist at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and lead author of the analysis in the Feb. 5 issue of the New England Journal of Medicine.

Based on that analysis and another recent review, the researchers also suggested that the "safe" period for combined use of progestin and estrogen to relieve postmenopausal symptoms was probably about two years, not the approximately five years researchers have discussed previously.

To get to the root of the drop in breast cancer cases, Chlebowski and his colleagues looked at data from the Women's Health Initiative (WHI) clinical trial (more than 15,000 women were assigned to either a placebo or HRT) and an observational study in which more than 25,000 women were on HRT, and more than 16,000 were not.

The part of the WHI that looked at combined hormone therapy was halted in 2002, as soon as researchers saw surprisingly higher rates of heart problems and breast cancer in women assigned to take the combined HRT (but not estrogen alone).

When Chlebowski's group looked in more detail and at shorter intervals for the effects of HRT, they found that during the initial two years, the HRT group participating in the clinical trial had fewer breast cancer diagnoses than the placebo group. However, the number of breast cancer cases in that group increased over the 5.6-year study period. The risk decreased rapidly in both groups after they stopped the pills, even though both groups had mammograms with similar frequency.

That fact weakens the argument that the drop in breast cancer cases was due to fewer women getting mammograms, he noted.

"There was a rapid decline in breast cancer incidence after stopping hormones, while mammography use didn't change between the groups," Chlebowski explained.

For instance, in the observational study, the incidence of breast cancer was about two times as high in the group on hormones as in the placebo group, but the difference faded about two years later, as women discontinued the hormones.

The bad news is that women who continue the combined HRT for about five years are at increased risk for breast cancer, the new analysis suggested.

"A woman who continues combined hormone therapy after about five years would double her personal annual risk of breast cancer," said Dr. Marcia Stefanick, a professor of medicine at Stanford University School of Medicine and a co-author of the analysis. That risk increases even when adjustments were made for age, which boosts risk on its own, she said. What happens with risk after that five years of use is not known, she said.

Another study, published online earlier this week in the journal Cancer, also finds that two years may be a "safe" period for the use of combined HRT. Eugenia Calle, former vice president of epidemiology for the American Cancer Society, and her colleagues looked at about 68,000 women who were cancer-free at the study's start in 1992, evaluating their hormone use and risk of getting breast cancer, and following them until mid-2005.

They found that the risk of breast cancer increased substantially after three years of using HRT -- for lobular cancer, the therapy doubled the risk at three years -- but there was no increased risk for those who used it for less than two years. However, Chlebowski said cancers may simply be harder to detect on mammograms during initial hormone use.

So what's the best advice on hormone use?

"Our paper suggests after starting estrogen plus progestin, you probably have two or three years where your risk isn't elevated," Calle told HealthDay. "And after that, your risk is elevated."

The new findings "add to a large accumulating volume of data," said Dr. Joann Elmore, a professor of medicine at the University of Washington, in Seattle. Overall, the data suggest that "the benefit of hormone therapy is less than we had hoped for, and there are risks that need to be considered." Each woman needs to weigh the risks and benefits, taking into account the severity of her symptoms, she added.

Chlebowski suggested that women consider stopping the hormones after two to five years and see if symptoms persist. "A truly safe interval can't be defined," he said.

More information

To learn more about HRT, visit the American Cancer Society.

SOURCES: Rowan Chlebowski, M.D., Ph.D., medical oncologist, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, Calif.; Joann G. Elmore, M.D., M.P.H., professor, medicine, University of Washington, Seattle; Marcia Stefanick, M.D., Ph.D., professor, medicine, Stanford University School of Medicine, Stanford, Calif.; Eugenia Calle, former vice president, epidemiology, American Cancer Society, Atlanta; Feb. 5, 2009, New England Journal of Medicine; Feb. 2, 2009, Cancer, online

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