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Post-menopausal hormones boost breast cancer risk, study finds

Soybeans contain estrogen-like compounds that may alleviate the symptoms of menopause. But new findings suggest women who take estrogen and progestin after menopause not only increase their chances of getting breast cancer but also may face a small increased risk of dying from the disease.
Soybeans contain estrogen-like compounds that may alleviate the symptoms of menopause. But new findings suggest women who take estrogen and progestin after menopause not only increase their chances of getting breast cancer but also may face a small increased risk of dying from the disease. (Knight-ridder)

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New research from a federal study has found that women who took hormones for menopause are more likely to get breast cancer.
By Rob Stein
Washington Post Staff Writer
Wednesday, October 20, 2010; 12:47 AM

Women who take a popular hormone replacement drug after menopause not only increase their chances of getting breast cancer but also seem to face an increased risk of dying from the disease, according to new results of a landmark federal study.

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The study of more than 12,000 women who were followed for about 11 years produced powerful evidence that deaths from breast cancer were more common among hormone-users, apparently because their cancers had already started to spread.

For years, doctors recommended that women take hormones to alleviate hot flashes and other symptoms of menopause to protect their hearts and generally remain more youthful. But eight years ago, the federally funded Women's Health Initiative revealed that hormones' benefits were outweighed by risks, including heart disease and breast cancer. Hormone use plummeted by more than half, although millions of women still take them.

Since then, women dealing with the life-changing effects of menopause have faced confusing information. Most experts recommend that women who need hormones take the lowest dose for the shortest period of time. Some say that it is safe to use hormones for up to five years; others say that remains unclear. Previous research indicated that the tumors in women who took hormones tended to be small and treatable and did not put them at greater risk of dying from the cancer.

The new analysis by the Women's Health Initiative, published in Wednesday's issue of the Journal of the American Medical Association, found that women who took the combination of estrogen and progestin - sold as Prempro - were more likely to have tumors that appeared to be larger, were often hard to treat and were more likely to have spread to their lymph nodes. But most important, their risk of death appeared elevated.

Coupled with research published last year that found that women who took hormones were about 70 percent more likely to die from lung cancer, the new findings underscore the risks posed by the therapy.

"Women taking estrogen plus progestin are at greater risk from dying from the two leading causes of cancer death in women," said Rowan T. Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, who led the analysis.

The new breast cancer findings surprised even some experts who have remained more supportive of hormone use.

"This really is a paradigm shift," said Hugh S. Taylor, chief of reproductive endocrinology at Yale University. "There was a whole group of people, including myself, who had been thinking hormone use was associated with an increased detection of breast cancer but not necessarily an increase risk of death from breast cancer. But this really nails it."

Although the study found that hormone use appeared to double the relative risk of dying from breast cancer, several experts stressed that the absolute risk was very low. In the new study, 25 women among those taking the hormones died from breast cancer, compared with 12 among those who took a placebo. The increased risk translates into 2.6 vs. 1.3 deaths from breast cancer each year for every 10,000 women taking hormones, or about 1.3 additional deaths, the study found.

"Let's not throw the baby out with the bath water," Taylor said. "Hormonal symptoms can really be life-changing for many women - changing their ability to concentrate, their mood, their personality. It can be really horrendous. Just because there is a very small risk associated with a therapy doesn't necessarily mean we completely abandon it."

In 2002, more than 110 million prescriptions for hormones were filled; by 2009, the number had dropped to about 40 million, according to IMS Health, which tracks prescription drug sales.

Breast cancer diagnoses subsequently started to drop. That appeared to help explain one of the biggest mysteries about breast cancer - why the number of cases rose steadily for decades: Hormone use probably played a key role, along with better detection by mammography and other factors.

Breast cancer survival has been rising because of earlier detection and better treatment. That trend could accelerate because of the millions of women who have stopped taking hormones, Chlebowski said.

Pfizer, which bought Wyeth in 2009, said the company continues to stand by the use of the hormones by some women. Wyeth made Prempro, the estrogen/progestin combination tested in the study.

"Hormone therapy is among the most thoroughly studied medicines and the increased risk for breast cancer compared to placebo has been included in Prempro's label since its introduction in 1995. This analysis does not alter that risk, nor does it dispute hormone therapy's effectiveness," the company said in a statement.

Chlebowski acknowledged that the risk in the study was low and barely met the threshold for being considered statistically significant. But he said he was confident that the risk was real, and others said the actual risk was probably far greater.

"I don't think there's any doubt here that there will be a clear deleterious effect here," said Peter B. Bach, an epidemiologist at Memorial Sloan-Kettering Cancer Center in New York who wrote an editorial accompanying the new report.

The new study found that 385 of the hormone users diagnosed with invasive cancer had taken hormones, compared with 293 of those who had taken a placebo. Eighty-one (23.7 percent) of the hormone users had cancer that had already spread to their lymph nodes, compared with 43 (16.2 percent) who had taken a placebo. In addition, there were 51 deaths for any reason from any cause among the hormone-users, compared with 31 among those taking a placebo, which translates into 5.3 vs. 3.4 deaths per 10,000 women per year.

"I don't mean to be alarmist, but when it comes to hormone replacement therapy, we've been wrong, wrong and wrong about this stuff," Bach said. "I just don't have the confidence to say that we know that any duration of therapy is safe."

Several experts stressed, however, that the breast cancer risk is not associated with estrogen use alone, which women who have had hysterectomies can take. But the new findings illustrate the urgency of determining whether women who start taking hormones when they are younger may avoid the increased risks and whether other hormone forms or delivery methods might be safer, they said.

"We need much more research on the role of the newer formulations being used by women, including lower doses of hormone and natural progesterone as opposed to synthetic progestin," said JoAnn E. Manson, chief of preventive medicine at Harvard's Brigham and Women's Hospital in Boston. "We don't know conclusively if those different formulations would confer less risk, but they may."


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