By Denise Grady, The New York Times
Published: October 19, 2010
Hormone treatment after menopause, already known to increase the risk of breast cancer, also makes it more likely that the cancer will be advanced and deadly, a study finds.
Women who took hormones and developed breast cancer were more likely to have cancerous lymph nodes, a sign of more advanced disease, and were more likely to die from the disease than were breast cancer patients who had never taken hormones.
The increased risks were relatively small and are not fully understood. But previous research has found that hormone treatment can cause delays in diagnosis by increasing breast density, making tumors harder to see on mammograms. Delayed diagnosis may increase the risk of death.
It is also possible that hormones may feed the growth of some breast cancers or the blood vessels that tumors need to grow and spread.
The treatment studied was the most commonly prescribed hormone replacement pill, Prempro, which contains estrogens from horse urine and a synthetic relative of the hormone progesterone.
Many doctors assume that women can safely take hormones for four or five years for menopause symptoms like hot flashes and night sweats, said Dr. Rowan T. Chlebowski, the first author of an article published this week in The Journal of the American Medical Association and an oncologist who treats breast cancer patients at the Harbor-U.C.L.A. Medical Center in Torrance, Calif.
“I don’t think you can say that now,” he said. “I know some people have to take it because they can’t function, but the message now is that you really should try to stop after a year or two.”
Dr. Chlebowski said it was not known whether there is any length of time for which these hormones can be taken without increasing breast cancer risk.
The new information comes from the continuing follow-ups with 12,788 women who were in the Women’s Health Initiative, a major federally financed study that compared women taking hormones with a group taking placebos. The study was halted in 2002, three years ahead of schedule, because researchers found that the hormones were causing small but significant increases in the risk of breast cancer, heart disease, strokes and blood clots in the lungs.
The 2002 study had a huge impact. Before it came out, there was a widespread belief that hormones would reduce women’s risk of heart disease and generally keep them youthful, sexy and healthy. For many, the study shattered that faith.
Six million American women had been taking hormones, but the number quickly fell by about half. The breast cancer rate also soon began to decrease, and many researchers attribute that to the drop in hormone use.
The new report increases the average follow-up time to 11 years from the original 5.6 years. It is the first report from the Women’s Health Initiative that includes death rates from breast cancer related to hormone use.
The researchers found small but significant increases in several harmful effects in women who took the hormones. As the study previously showed, women taking hormones are more likely to develop invasive breast cancer. Their rate of the disease was 0.42 percent per year, compared with 0.34 percent per year in the placebo group.
Among women with breast cancer, those who took hormones were more likely to have cancerous lymph nodes, a sign of more advanced disease — 23.7 percent, versus 16.2 percent in the placebo group.
More women who took hormones died from breast cancer — 0.03 percent per year, versus 0.01 percent per year in the placebo group. That translates to 2.6 deaths per 10,000 women per year among those taking hormones, twice the 1.3 deaths per 10,000 in the placebo group.
Among women who had breast cancer, those who took hormones also had a higher death rate from other causes — 0.05 percent per year, versus 0.03 percent per year. In other words, there were 5.3 versus 3.4 deaths per 10,000 women per year — 1.9 extra deaths in hormone users.
Dr. Chlebowski said that a report last year from the Women’s Health Initiative also found that although hormone treatment did not increase women’s rate of lung cancer, hormone use was linked to a higher death rate among women who had the cancer.
Another author of the new study, Dr. JoAnn E. Manson, a professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, said women should not take the hormones at all unless they really need them, for moderate to severe symptoms like hot flashes and night sweats that disrupt sleep and severely affect their quality of life.
At the same time, she said, the new information should not necessarily alarm women who have taken the hormones, because the new report found only one to two additional breast cancer deaths per 10,000 women per year among those taking hormones.
“The data suggest it is cumulative long-term use,” Dr. Manson said. “Women should avoid long-term use. I think that’s the bottom line.”
She said that women who want treatment should take the lowest possible dose that eases their symptoms.
Noting that many women are taking other hormone formulations in hope of avoiding Prempro’s risks, Dr. Manson said that little was known about the drugs and that more research was urgently needed.
She said more research was also needed to find out if women who took hormones early in menopause had the same risks as those who started the drugs later.
Pfizer, which makes Prempro, issued a statement saying it took the new findings seriously, but questioned the mortality figures.
An editorial accompanying the journal article said that the researchers had probably underestimated the increase in deaths from breast cancer due to hormone therapy, and that “with longer follow-up, the deleterious effect will appear larger,” even though the women are no longer taking the drugs.
The editorial writer, Dr. Peter B. Bach, a physician at Memorial Sloan-Kettering Cancer Center in New York, said that although the increase in cancer in the study might seem small, it becomes large when multiplied out over the population. He also questioned the advice being given to women, to consult their doctors about risks and benefits, and to take the lowest possible doses for the shortest possible time.
“The fallback is that doctors and patients should be deciding this on a one-to-one basis, weighing risks and benefits,” Dr. Bach said in an interview. “How do you do that when you don’t know what the risks are?”
He added, “If you care about preventing this disease and keeping women from suffering and dying from it, then it’s hard to look at these drugs and not have serious concerns about them being used, even for what are intended to be relatively short periods of time.”
This article has been revised to reflect the following correction:
Correction: October 19, 2010
An earlier version of this article incorrectly described Dr. Peter B. Bach, writer of an editorial in The Journal of the American Medical Association. He is a physician at Memorial Sloan-Kettering Cancer Center, but he is not an oncologist.
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