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Women who take the drug tamoxifen after having cancer removed from one breast may run a higher risk of developing a relatively more dangerous form of cancer in the other breast, according to a new study.

The findings contradict previous research and are drawn from the analysis of a small number of patients, which increases the chance they may be a fluke.

“This is a preliminary study. My colleagues and I do not think these findings should change current therapy,” said Christopher Li, an epidemiologist at the Fred Hutchinson Cancer Research Center in Seattle. He said he hoped the results would stimulate further research on tamoxifen, a drug that blocks the action of the hormone estrogen and which has had a roller-coaster reputation over the last two decades.

More than half of the nearly 200,000 American women newly diagnosed with breast cancer each year will eventually take tamoxifen. The drug’s purpose is to suppress the growth of any cancer cells that may remain after the original tumor is surgically removed. A secondary goal is to prevent any new cancers from developing in the untreated breast.

Tamoxifen’s usefulness in performing both tasks is unquestioned. An analysis of 55 studies enrolling a total of 37,000 patients recently showed that taking the drug for five years cut by nearly half the chance that a woman’s original cancer would recur or that a new tumor would arise.

The new study, published Wednesday in the Journal of the National Cancer Institute, examined the experience of about 9,000 women from the state of Washington who were treated for breast cancer during the 1990s. It compared the experience of those who took tamoxifen and those who didn’t.

Estrogen stimulates the growth of breast cells because the cells carry molecular receptors that capture the hormone molecule and permit it to work. About 70 percent of breast cancers have estrogen receptors (are called “ER-positive”), while 30 percent don’t have them (“ER-negative”).

Tamoxifen blocks the receptor, preventing estrogen from landing and stimulating cell growth. ER-negative breast cancers, however, are impervious to the effects of tamoxifen, and in general are harder to treat than ER-positive tumors largely for that reason. Women whose tumors are ER-negative have a poorer prognosis, and up to a 30 percent higher risk of dying in the five years after initial diagnosis, compared to women with ER-positive cancers.

Among the Washington women, the risk of developing a new, second cancer in the opposite breast was extremely low overall. However, among the women who did develop new cancers in their opposite breasts, the tumors were much more likely to be ER-negative in the women taking tamoxifen than in the women not taking the drug.

The specific numbers were these. Of about 4,600 women using tamoxifen, there were 64 new tumors in the untreated breast, and 17 were ER-negative. Of about 4,300 women not using tamoxifen, there were 68 tumors, and 3 were ER-negative.

Whether the women with the ER-negative tumors fared poorly, or were more likely to die soon, is not known. Li and his colleagues didn’t collect that data, and in many cases too little time has passed for a difference to be detected.

There are few studies in which the presence or absence of estrogen receptors in new tumors of the opposite breast was recorded for large populations of women. The current envidence (some of it not yet published) is that tamoxifen neither harms nor helps women with ER-negative tumors. The study by Li suggests otherwise: that tamoxifen may stimulate the growth of ER-negative cells.

Kent Osborne, a prominent breast cancer researcher at the Baylor College of Medicine in Houston, questioned the findings. The study was not a randomized, controlled trial, which is the kind best able to reduce the risk of misleading results. More important, Osborne said, was the fact that Li’s study found that tamoxifen had only a slight effect in preventing new tumors in women whose original cancers were ER-positive.

“That immediately raises questions about the validity of this data,” he said.

This skepticism was shared by Sandra Swain, chief of the medicine branch of the National Cancer Institute, who wrote an editorial in the journal commenting on the study.

While she said the Seattle researcher team “is a very credible group,” the small number of cases in the study makes the results statistically shaky.

“I just don’t put any faith in the results,” she said. “The results of this study should not change practice at all. Women should not be afraid to take tamoxifen based on this study.”

Tamoxifen’s benefits, however, have been revised over the years, sometimes unexpectedly.

Studies in the 1990s showed that while the drug is very helpful, taking it for more than five years isn’t a good idea. Longer exposure can, paradoxically, raise a woman’s risk of breast cancer. It’s also now clear that tamoxifen increases the risk of uterine cancer. That tumor, however, relatively rare, and in women with breast cancer the drug has a clear net benefit on survival.

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