Aspirin, other NSAIDs and cancer prevention: Where are we now?

PL02-04 Aspirin, other NSAIDs, and cancer prevention - where are we now? Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, inhibit a wide variety of cancers in animal models, an effect usually attributed to inhibition of COX-1 and COX-2 activity. A relatively recently developed class of NSAIDs, selective COX-2 inhibitors, have been proven in randomized trials to substantially reduce colorectal polyp recurrence in humans. However, these same randomized trials showed that selective COX-2 inhibitors can increase risk of cardiovascular events, resulting in withdrawal of some COX-2 inhibitors from the U.S. market, and greatly limiting their use as cancer prevention agents. Considerable evidence indicates that other non-aspirin NSAIDs may also increase risk of cardiovascular events. These results have refocused attention on aspirin as a potential cancer prevention agent. Aspirin, unlike other NSAIDs, has antithrombotic effects and is already widely used to prevent cardiovascular disease, although often at doses (e.g. 81 mg/day) that may be of limited value in cancer prevention. Over the last nearly 20 years, a large number of observational epidemiologic studies have examined the association between regular use of aspirin, usually adult strength aspirin (e.g. 325 mg tablets), and risk of individual cancers. In these studies, aspirin use has consistently been associated with reduced risk of colorectal cancer. Randomized trials have also shown that aspirin reduces colorectal polyp recurrence. Observational studies of aspirin use and risk of other common cancers have not produced consistent results. However, a considerable number of studies have reported modest reductions in risk of breast and prostate cancer, the most common cancers among U.S. women and men. More recent studies on aspirin and cancer have highlighted the importance of dose and duration. The Women’s Health Study, a 10 year long randomized trial of low dose aspirin (100 mg every other day), observed no reduction in risk of any cancer. In contrast, a significant reduction in risk of colorectal cancer was observed in a recent analysis including long-term post-intervention follow-up from two early randomized trials of at least 300 mg/day of aspirin for cardiovascular disease prevention. No reduction in risk of other cancers was observed. In a large observational study (the Cancer Prevention Study II Nutrition Cohort), daily use of adult-strength aspirin (> 325 mg) for 5 or more years was associated with an approximately 15 percent reduction in risk of total cancer incidence in both men and women, driven mainly by reduced risk of colorectal, prostate, and possibly breast cancer. Current clinical recommendations for use of aspirin for disease prevention are appropriately based on balancing the known reduction in risk of cardiovascular events against the known increased risk of serious gastrointestinal bleeding, without regard to cancer risk. While there is relatively strong evidence that aspirin can reduce colorectal cancer risk, a reduction in risk limited to one cancer is unlikely to be sufficiently important to be considered when making clinical decisions about aspirin use. The session will include a discussion of what types of research are needed to best determine if and how cancer prevention should be taken into account when making decisions about who should use aspirin and at what dose.