Cancer Risk of Hormones May Linger

By GINA KOLATA

ETHESDA, Md., Oct. 23 — Scientific evidence has not shown that women can avoid the breast cancer risk from hormone replacement therapy by taking the drugs for only a short time, researchers said today. It also has not shown that the risk disappears as soon as the drugs are stopped.

The questions about when the risk develops and how long it lasts arose after a large federal study of hormone replacement therapy reported in July that the drugs' risks, including a slight increase in the incidence of breast cancer, were not exceeded by their benefits.

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The study was halted after five years when researchers found that the women taking hormones had a clear increase in their incidence of breast cancer.

At a meeting here today, sponsored by the National Institutes of Health, Dr. Rowan T. Chlebowski, of the Harbor-U.C.L.A. Research and Education Institute, reported that even women who took the hormones for some period but then stopped had more breast cancer than those who never took the hormones.

Their increased risk was about equal to that reported for the entire study: hormone therapy would result in an extra 8 out of 10,000 women per year being found to have breast cancer.

But, Dr. Chlebowski added, to rigorously test whether the cancer risk occurs with shorter term use scientists will have to conduct another study, with some women taking the drugs for one year, some for two, some three, and so on.

Dr. Richard Hodes, the director of the National Institute on Aging, said, "People who are presuming that there is no increased risk unless you have been taking hormones for four or five years are overinterpreting what the study says."

The federal study's findings were a shock to many of the six million American women who were taking the study drug, Prempro, which is a combination of estrogen and progestin.

The drug's maker, Wyeth, says sales have fallen by 40 percent but added that it did not know how many who dropped Prempro were taking another company's hormone replacement drug and how many had stopped taking hormone replacement altogether.

The study, known as the Women's Health Initiative, involved 16,000 postmenopausal women. Half were assigned to take Prempro and the others took a placebo.

The study, which had been scheduled to continue until 2005, was stopped in July because scientists noticed that the women taking hormone replacement therapy were at slightly increased risk of breast cancer, heart attacks, strokes and blood clots and that those risks were larger than the drugs' benefits, a slight decrease in hip fractures and in colon cancer.

But as many as 40 percent of the women in the study had already stopped taking their medications, with some having taken them for months and others for years. When Dr. Chlebowski looked at what had happened to that group, he found that its members had the same additional risk of breast cancer as women who had taken Prempro faithfully from when they joined the study until the day they were told to stop.

Dr. Chlebowski and others also cautioned against assuming that the risks of hormone replacement therapy end when a woman stops taking the drugs. He said other hormone treatments can have delayed and lasting effects.

Women who take the drug tamoxifen, which blocks estrogen's effects in the breast, for five years and then stop are protected from breast cancer for another decade, Dr. Chlebowski said. But tamoxifen also increases the risk of cancer of the uterine lining, and women who take the drug for five years and then stop are at increased risk for this cancer for another decade, he said. The women in the Women's Health Initiative study will be followed for years, he said, which should eventually determine if the breast cancer risk lingers, and, if so, for how long.

Some doctors have asserted that it is safe to give hormone replacement therapy to women who are not at high risk of breast cancer. But, Dr. Chlebowski said, there is no good way to identify women whose risk is low. Other studies have indicated that the usual way of tallying risk factors, like age at menstruation, have not been particularly effective in determining a woman's risk.

The message that it was impossible to pick out individuals most likely to be harmed or benefited by hormone replacement therapy was one that many doctors, researchers and drug company executives in the crowded meeting today did not welcome. In politely phrased questions in the public sessions and in heated discussions in hallways, many audience members repeatedly asked the scientists to explain.

Some, like Dr. Otis Brawley, a cancer researcher from Emory University, said that many doctors and medical experts were being inconsistent. The Women's Health Initiative, he said, pointed to an excess risk of 8 new breast cancers per 10,000 women per year. Some women's doctors have told them that that risk is tiny.

But, Dr. Brawley said, mammogram screening, at best, prevents one breast cancer death per year out of every 17,000 women over age 50 who are screened. The figure is even lower for women in their 40's — one out of every 25,000. Yet doctors and public health officials have said mammograms are vitally important in the fight against breast cancer. They cannot have it both ways, Dr. Brawley said.