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The results of a breast cancer study by epidemiologists from the Mailman School of Public Health and Weill Cornell generated nothing less than a media storm when they were published in JAMA in May. The finding that women who regularly take aspirin seem to be at lower risk of breast cancer was picked up by more than 1,300 print and broadcast media.

The study found that women who take aspirin every day are 25 percent less likely to develop breast cancer than women who never use aspirin, consistent with previous research suggesting a risk reduction between 20 percent and 40 percent.

Unlike other studies, however, the new research shows that aspirin's protective effect is limited to frequent users and to hormone-positive cancers, whose growth is promoted by estrogen or progesterone. The study was published in the May 27 issue of the Journal of the American Medical Association.

Despite the findings the authors do not advocate women become regular aspirin users to ward off breast cancer. "No one is recommending aspirin to prevent any kind of cancer yet. The cumulative evidence isn't strong enough, and it should be remembered that aspirin has side effects, such as gastrointestinal toxicity," says Dr. Alfred Neugut, the study's senior author, professor of epidemiology in Mailman and medicine at P&S. "But if you're already using aspirin to prevent a heart attack or stroke, this may turn out to be icing on the cake."

Instead of advocating widespread aspirin use, the study's lead author, Dr. Mary Beth Terry, assistant professor of epidemiology in Mailman, says the study's findings confirm the research team's hypothesis about how aspirin reduces breast cancer risk, which then could be used to develop safer, more effective chemoprevention strategies.

The hypothesis stems from laboratory research by one of the study's other authors, Dr. Andrew Dannenberg of Cornell, who found that breast cancers in mice produced excess amounts of the COX-2 enzyme, a key promoter of inflammation. COX-2 also ramps up the synthesis of the hormones estrogen and progesterone. The two hormones encourage the growth of tumors that contain receptors for estrogen or progesterone but have no effect on receptor-negative tumors. If aspirin, an inhibitor of COX-1 and COX-2 enzymes, can reduce the risk of breast cancer as other studies have shown, the researchers hypothesized that it should only decrease the risk of hormone-positive tumors.

In the study, the researchers looked at the use of two general COX inhibitors – aspirin and ibuprofen – and the use of a different painkiller, acetaminophen, among 1,442 women recently diagnosed with breast cancer and 1,420 women without breast cancer. The data comes from the Long Island Breast Cancer Study Project, a 10-year study led by epidemiologist Dr. Marilie Gammon of the University of North Carolina.

As predicted, the results found aspirin's effect on cancer was limited to hormone-positive tumors. About 70 percent of breast cancers are hormone-positive, which are easier to treat, because cutting off the effects of hormones – usually with the drug tamoxifen – can shrink the tumors.

The strongest effects of aspirin were seen in daily users who averaged about 25 percent fewer breast cancers than nonusers. Less frequent use did not provide any protection, nor did daily use of aspirin more than five years previously.

"It's similar to aspirin's cardiovascular effects," Dr. Neugut says. "As long as you use it you're protected; once you stop, it goes away." But he added that the study could not tell whether the low-dose aspirin (81 mg.) used to prevent heart attacks would be sufficient to reduce breast cancer risk, since the researchers did not ask for dose information.

The other general COX inhibitor, ibuprofen, showed similar trends, but far fewer women in the study used the painkiller and the results were not statistically significant. Acetaminophen, which does not alter COX activity, had no effect on breast cancer risk.

A clinical trial is now under way in Canada to see if more selective COX-2 inhibitors can reduce breast cancer rates in postmenopausal women at high risk of developing breast cancer.

The study was funded by the National Cancer Institute and the National Institute of Environmental Health.

–Susan Conova



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