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Use of Non-steroidal Anti-inflammatory Drugs Dramatically Reduces Risk of Breast Cancer: Presented at AACR

By Cameron Johnston

TORONTO, ON -- April 8, 2003 -- Women who use non-steroidal anti-inflammatory drugs (NSAIDs) on a regular basis and over an extended period of time appear to have a significantly lower risk of developing breast cancer, according to an analysis of data from the Women's Health Initiative (WHI).

The findings from the observational WHI study were scheduled to be presented here April 5^th-9^th at the Annual Meeting of the American Association for Cancer Research, which was cancelled because of the outbreak of the severe acute respiratory syndrome in Toronto recently. Instead, the analysis was presented April 8^th in a conference call with medical reporters.

Dr. Randall Harris, a professor of medicine, epidemiology and biostatistics, Ohio State University, in Columbus, Ohio, said the latest results from the far-reaching WHI show that women who took aspirin, ibuprofen or related compounds for 5 to 9 years had a 21% reduction in breast cancer risk. Women who took them for 10 years or more had a 28% reduction in the risk of breast cancer. These points were all statistically significant, as was the trend that suggests the risk of cancer diminished the longer the woman takes an NSAID.

Of the 80,741 women between the aged of 50-79 who were followed for a mean of 4 years, there were 1,392 confirmed cases of breast cancer, for an overall annual incidence of 481 cases per 100,000 women per year. This was in keeping with the national average in the US, Dr. Harris said.

Dr. Harris said a striking finding in the study was that long-term ibuprofen users reduced their risk of cancer by just over 49%.

"We observed these effects with regular intake of standard doses -- 325 mg of aspirin and 200 mg of ibuprofen, at least three times per week." He added, however, that no comparable effect was seen among women who used so-called "baby aspirin" at 81 mg per day, or among those who used acetaminophen.

"These protective effects were consistent in high risk women -- those with a family history [of breast cancer], those on estrogen replacement therapy and those in the highest quartile of body mass," he added.

As Dr. Harris explained, aspirin-like compounds work by blocking the cyclo-oxygenase-2 (COX-2) enzyme, which he called the "trigger gene" for inflammation. In doing so, these agents also block several key steps in cancer development, including cell mutation, division of cancer cells, and angiogenesis-- which promotes metastases -- and they promote apoptosis.

"Most importantly, there is a key link between COX-2 and the dys-regulation of estrogen production in the mammary glands, and these compounds -- such as aspirin and ibuprofen -- break that link. Acetaminophen does not block COX-2 and it did not show an effect in our study," he said.

"Our results revealed significant reductions in the incidence of breast cancer among women who took aspirin and ibuprofen for more than 5 years. Intake of any aspirin-like compound for 10 or more years resulted in a 29% risk reduction and long term ibuprofen use reduced the risk of breast cancer by around 50%."

"The evidence from molecular studies, animal studies, and epidemiological studies such as this one is compelling and converging that relatively harmless and inexpensive compounds, already used by millions, reduce the risk of breast caner as well as other forms of cancer," he said.

He concluded that this study paves the way for the start of randomly controlled trials that will evaluate aspirin and ibuprofen, and other COX-2 inhibitors in cancer prevention therapy.

The WHI was supported by the National Cancer Institute, the National Health Lung and Blood Institute, and the National Institutes of Health.

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