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Women who regularly take aspirin seem to be at lower risk of the most common type of breast cancer than those who do not take aspirin, report researchers from Columbia University's Mailman School of Public Health and College of Physicians Surgeons, Weill Cornell Medical College, and NewYork-Presbyterian Hospital. Specifically, aspirin may cut the risk of hormone receptor positive breast cancer, which makes up about 60-70% of all breast cancer cases.

The study, conducted in nearly 3,000 women in Long Island, New York from the Long Island Breast Cancer Study Project, headed by Dr. Marilie Gammon of the University of North Carolina and Lineberger Cancer Center is to be published May 26 in the Journal of the American Medical Association.

Mary Beth Terry, Ph.D., of Columbia University Mailman School of Public Health is the lead author, with Alfred I. Neugut, M.D., Ph.D., of Columbia University College of Physicians Surgeons and Mailman School of Public Health, and Andrew Dannenberg, M.D., of Weill Cornell Medical College as co-investigators.

The study suggests that the use of aspirin on a regular basis can reduce the risk of developing breast cancer, said Dr. Alfred I. Neugut, professor of Medicine and Epidemiology at Columbia University, and co-director of the Cancer Prevention Program at NewYork-Presbyterian Hospital. This is among the best empirical studies that has looked at this issue. What's more, it's the first to suggest that aspirin may be more effective at preventing certain types of breast cancer than others.

The study results add further to our knowledge base regarding the potential anticancer properties of nonsteroidal anti-inflammatory drugs (NSAIDs), said lead author Dr. Mary Beth Terry, assistant professor of Epidemiology at Columbia University Mailman School of Public Health. The benefits of aspirin use are still primarily for heart disease prevention and arthritis, but aspirin does have side effects. In women who are using it for appropriate purposes, there may be additional benefits in terms of breast cancer prevention.

An agent that is commonly used for cardiovascular protection seems to protect against another disease, hormone receptor positive breast cancer, said Dr. Andrew Dannenberg, the Henry R. Erle, M.D.-Roberts Family Professor of Medicine at Weill Cornell Medical College, and co-director of NewYork-Presbyterian Hospital's Cancer Prevention Program. From a public health perspective, this may representan additional benefit to those who need to take aspirin for other reasons, such as cardiovascular disease or arthritis. It could be a widely accessible benefit,even in developing countries, because aspirin is so inexpensive.

The research team analyzed data from 1,442 breast cancer patients and 1,420 healthy women that were collected in 1996 and 1997. The women were asked about their use of aspirin, ibuprofen, and acetaminophen (the active ingredient in Tylenol®). Aspirin and ibuprofen are NSAIDs. Acetaminophen is a pain reliever, but it is not an NSAID.

Overall, 21% of breast cancer patients and 24% of healthy women said they used aspirin at least once a week for the past six months or longer. When the researchers compared women with breast cancer to women who were cancer-free, they found that those who took aspirin regularly had a 26% lower risk of hormone receptor positive breast cancer compared with women who did not take aspirin.

The association was strongest in women who took seven or more aspirin tablets per week; and was greater in menopausal women than in their premenopausal counterparts. Aspirin users had the same risk of hormone receptor negative breast cancer as women who did not take the NSAID. And acetaminophen use was not associated with a reduced risk of breast cancer. Not enough women took ibuprofen to determine if there was a benefit, according to the report. Overall, 12% of women with breast cancer and 14% of those without breast cancer took ibuprofen on a regular basis.

About 60-70% of all breast tumors contain hormone receptors and will grow when exposed to either estrogen, progesterone, or both. Hormone receptor positive breast cancer is easier to treat, because cutting off the effects of estrogen usually with the drug tamoxifen can shrink the tumors.

However, it's too early to recommend that women start taking aspirin to prevent breast cancer. The study is retrospective, a design in which the researchers asked women to remember the details of their past aspirin use, which can be prone to error. And the researchers did not ask the women what dose of aspirin they took.

Many studies have suggested that NSAIDs may have anticancer properties.

There is considerable evidence that NSAIDS protect against colorectal cancer and cancers of the upper gastrointestinal tract. And there are several studies that have demonstrated that NSAIDS also reduce the risk of breast cancer,the focus of our research, the authors said.

Aspirin and other NSAIDs suppress an enzyme known as cyclooxygenase (COX), which plays a key role in the production of molecules known as prostaglandins. Studies in animals have shown that one type of prostaglandin, PGE2, induces an estrogen-synthesizing enzyme called aromatase.

We postulated that if that mechanism were the same in humans, then aspirin,an inhibitor of PGE2 production, should protect better against hormone receptor-positive than hormone receptor-negative breast cancer, and that is what we found, said Dr. Dannenberg. From my standpoint, the ability to translate a preclinical finding to the clinic is very, very exciting and a point of distinction. To our knowledge, this is the first study where an understanding of a specific COX-dependent mechanism has led to the identification of a subset of patients who benefit from aspirin or NSAID use.

While tamoxifen is known to help prevent hormone receptor positive breast cancer from recurring, aromatase inhibitors appear promising as well.

Aspirin, ibuprofen, and other NSAIDs, such as diclofenac and naproxen, inhibit two different COX enzymes known as COX-1 and COX-2. Newer drugs, such as celecoxib and rofecoxib, inhibit just the COX-2 enzyme.

Inhibitors of COX-2 such as celecoxib are widely used by post menopausal women to treat arthritis, said Dr. Neugut. The results of this study suggest that these agents might protect against breast cancer.

Study collaborators include Fang Fang Zhang and Heba Tawfik of Columbia University Mailman School of Public Health; Kotha Subbaramaiah of Weill Cornell Medical College; Marilie Gammon of University of North Carolina (Chapel Hill); and Susan Teitelbaum and Julie Britton of Mt. Sinai School of Medicine (New York City).

The study was funded in part by grants from the National Cancer Institute and the National Institute of Environmental Health.