Study Shows HRT Even Riskier Than Thought

TUESDAY Oct. 19, 2010 -- Not only does prolonged use of hormone replacement therapy raise the risk of breast cancer, new research finds, but it also ups the risk for more severe forms of the disease and increases a woman's chances of dying.

A study appearing in the Oct. 20 issue of the Journal of the American Medical Association is at odds with previous observational studies that had suggested a raised risk of breast cancer, but only for less aggressive and more treatable tumors. The researchers added that this is the first time an increase in mortality has been shown.

The findings apply only to estrogen-plus-progestin, or combined hormone therapy, not estrogen-alone therapy.

"It looks like all categories of breast cancer are increased," said study author Dr. Rowan Chlebowski. "The preponderance of observational studies had suggested that the cancers would have a more favorable outcome but now we're seeing all categories of cancer increasing and, for the first time, we're reporting mortality."

The findings may raise the bar for clinicians counseling patients about the use of postmenopausal hormone replacement therapy (HRT), or at least the combined form of the therapy.

"It definitely affects how we counsel people," said Dr. Elizabeth Poynor, a gynecologic oncologist and pelvic surgeon at Lenox Hill Hospital in New York City. "The only reason to go on HRT now is to control symptoms of menopause in women who can't have their symptoms controlled by non-hormonal methods. The risk-benefit is always highly individualized, so this will definitely be a component of my conversations with my patients moving forward."

"This reinforces the message that women should take the lowest dose possible for the shortest duration possible," added Chlebowski, who is a medical oncologist with the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. "Maybe women should consider talking to their physician about stopping after a certain period of time on hormone therapy."

The now legendary Women's Health Initiative (WHI) was abruptly halted in 2002 after researchers reported an increased incidence of breast cancer in women taking combined estrogen-plus-progestin.

The original WHI involved 16,608 postmenopausal women aged 50 to 79 who still had their uterus. Participants were randomly assigned to take combined HRT or a placebo.

Now, with 11 years of total follow-up, Rowan and his colleagues found that women taking the combined HRT were 25 percent more likely to have an invasive breast cancer than women in the placebo group, were 78 percent more likely to have cancer that had spread to the lymph nodes and were almost twice as likely as the placebo group to die of breast cancer. They were also 57 percent more likely that women in the placebo group to die from any cause after receiving a diagnosis of breast cancer.

Put another way, there were more deaths from breast cancer (2.6 vs. 1.6 deaths per 10,000 women per year) and more deaths from any causes (5.3 vs. 3.4 deaths per 10,000 women per year), respectively, in the HRT group compared to the women taking a placebo.

Hormone replacement therapy use did drop off after the surprise 2002 findings, from 35 percent to 40 percent of postmenopausal women to about 15 percent to 20 percent, Chlebowski said.

"But that is still tens of millions of prescriptions per year," he said.

And pushing the numbers down further in the United States (many other countries already have dramatically lower rates of use) will require some work, Chlebowski said.

"The gynecological community has been prescribing this for years, and for years it was thought to be beneficial [on heart risk, for instance]," he said. "The conjugated equine estrogens [used in combination with progestin in this study] were introduced into U.S. practice in 1942, so that's a long time."

But, to many experts, the risks seem more apparent than ever.

"This study goes even further to discourage the use of HRT in any manner that's not respectful of the downside," said Dr. Freya Schnabel, director of breast surgery at NYU Langone Medical Center in New York City. "The WHI had returned hormone therapy to the realm of medicine, not jelly beans. It's medication that has to be viewed in the exact same context of risks and benefits, indications and contraindications. There is a real downside to taking HRT, and getting breast cancer is not a trivial matter at all."

More information

Visit the U.S. National Heart, Lung, and Blood Institute for more on the Women's Health Initiative.

Posted: October 2010


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