Combination hormone replacement therapy appears to have a more threatening effect on breast cancer risk than previously known, according to a new study. The finding gives women another potentially serious health consequence to consider if they’re thinking about starting hormones or continuing treatment.

The study, published in the Journal of the American Medical Association (Vol. 289, No. 24: 3243-3253), is a new analysis of data collected during the Women’s Health Initiative, a randomized controlled trial comparing the effects of combination hormone therapy (estrogen plus progestin) with placebo. The drugs are sometimes prescribed to combat troubling symptoms of menopause like hot flashes and night sweats.

The WHI was designed to find out whether taking hormones could improve a woman’s overall health. More than 16,000 postmenopausal women ages 50-79 took part. The trial was stopped ahead of schedule in 2002 when researchers found that taking hormones actually increased the risk of certain chronic diseases, including breast cancer.

The new analysis shows that not only do women who take hormones have a 24% greater risk of getting breast cancer, but their cancers were harder to detect and were found at a more advanced stage. In addition, their risk rises much sooner than previous studies had suggested: after as little as five years of therapy.

“The consensus from most of the existing information (about hormone therapy and breast cancer) was that cancers didn’t develop early, and the ones that did would be early stage, with a favorable prognosis and easy to treat,” said Rowan T. Chlebowski, MD, PhD, lead author of the study. “We saw the opposite.”

In the study, women on combined hormone therapy developed more invasive cancers than women on placebo. Even worse, the tumors weren’t detected until they were larger and at a more advanced stage, making them harder to treat.

Another troubling finding: Women taking hormones had more abnormal mammograms, even after using hormones for as little as one year.

Although this study did not measure breast density, previous research has shown that combination hormone therapy is associated with increased breast density, which can make mammograms harder to read. A difficult-to-read mammogram makes breast cancer harder to detect.

It also can lead to false-positive findings: something that looks like a tumor but turns out not to be when further tests are conducted. Chlebowski worries that false-positive results could discourage women from getting subsequent mammograms, potentially delaying diagnosis of breast cancer even further. Peter Gann, MD, and Monica Morrow, MD, of Northwestern University, who wrote an editorial accompanying the study, also point to this as a potential problem.

Robert Smith, PhD, director of cancer screening for the American Cancer Society, thinks it is unlikely that false-positive mammogram results will discourage women from regular screening. But it should make them think twice about hormone therapy.

“The added risk of breast cancer, and the apparent reduction in the effectiveness of breast cancer screening, should discourage women from taking combination progestin and estrogen hormone therapy,” he said.

Chlebowski, a medical oncologist at Harbor-UCLA Research and Education Institute in Torrance, California, agrees that the study results complicate the risk-benefit analysis for women who are currently taking hormones or considering starting them.

Although factors like family history or certain genetic mutations may have a greater effect on breast cancer risk than hormone use, taking hormones is a choice, unlike those other factors, Chlebowski noted. There’s also the previously unknown risk of abnormal mammograms to consider now, he said. And hormone therapy also increases the risk of other health problems, including strokes and pulmonary embolisms, Chlebowski pointed out.

A woman suffering severe menopausal symptoms may decide the relief hormone therapy provides is worth the increased risk of breast cancer and other disease, he explained. But women with moderate or mild menopause symptoms may decide they’d rather put up with their discomfort.

This new analysis shows that trying to treat chronic health conditions with hormonal therapy is a tricky – and potentially dangerous – proposition, editorialists Gann and Morrow said. Although more studies are needed to clarify the risks of short-term use of combination hormone therapy, they added, this data provides “further compelling evidence against the use of combination estrogen plus progestin hormone therapy.”