Aspirin: Can Such a Commonly Used Drug Have an Impact on Cancer?

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Raymond DuBoisRecent findings published in the Journal of Clinical Oncology suggest that aspirin may play a role in reducing the recurrence of breast cancer in women who have been treated for that disease.


Dr. Michelle Holmes of Brigham and Women's Hospital in Boston and her colleagues studied self-reported data from 4,164 nurses who had an earlier diagnosis of breast cancer. They found that nurses who reported taking aspirin two to five days a week (often for problems unrelated to breast cancer) were 60% less likely to have a recurrence of breast cancer than their counterparts who did not take it, and 71% less likely to die from the disease.


Based on this study, scientists can't confirm a direct cause-effect relationship between lower breast cancer recurrence and aspirin use. However, it has stimulated a lot of discussion about the role of inflammation and anti-inflammatory drugs, like aspirin, on cancer.


Inflammation can open window

Inflammation is the body's response to an assault, such as an injury or infection. The body retorts by producing chemicals that signal immune cells to rise up, attack and kill the invading germs. Unfortunately, in the process they also can damage surrounding tissue, leading to pain and redness, and in some cases of chronic inflammation, open a window for uncontrolled cell growth -- which is cancer.


Certain drugs known as NSAIDs (non-steroidal anti-inflammatory drugs), including aspirin, ibuprofen and other over-the-counter and prescription medicines, have been known to reduce inflammation. Since the 1970s, we have known that these drugs work by inhibiting the production of prostaglandins, body chemicals that are necessary for blood clotting and that also sensitize nerve endings to pain.


NSAIDs can block two different cyclooxygenase (COX) enzymes, COX-1 and COX-2, which are produced by the body at sites of inflammation and also are produced by some precancerous tissues. COX-1 and COX-2 are key players in the conversion of certain fatty acids into prostaglandins, which in turn are associated with inflammation.


Aspirin and other aspirin-like drugs (called NSAIDs) can block both COX enzymes. However, they also can cause medical problems, such as stomach bleeding, when taken regularly for long periods of time. To try to circumvent these side effects while still providing relief against inflammation, in the early 1990s pharmaceutical companies began developing NSAIDs that inhibit only COX-2 enzymes (sometimes called COXIBs) and were marketed as Celebrex.


NSAID-cancer prevention connection

The connection between NSAID use and cancer prevention has been studied for a few decades. Scientists conducted a series of animal experiments to see if NSAIDs might inhibit the occurrence or growth of colorectal cancers. They found that, in fact, the colorectal tumors regressed in animals given NSAIDs. Later, randomized clinical human trials established that two NSAIDs (sulindac and celecoxib) suppressed adenomatous polyps and caused existing polyps to regress in patients with familial adenomatous polyposis (FAP, a rare hereditary condition).


The next step was to see how these medicines might affect people who didn't have FAP but might still be at risk for colon cancer. During the 1980s, epidemiologists began collecting evidence from population studies showing that people who reported regular NSAID use had a lower incidence of adenomatous polyps and lower colorectal cancer death rates. These results indicated a possible protective effect against colon cancer from NSAIDs for the general population.


In my laboratory in the early 1990s, we began investigating why NSAIDs might convey this protective effect. My research team and I discovered that some intestinal epithelial cells made significant amounts of the COX-2 enzyme in response to growth factors or tumor initiators. This led us down a path of discovery that connected the two and helped explain, in part, how selective COX-2 inhibitors can reduce the risk of some cancers in people.


Scientists moved forward to test this theory in human patients. Two randomized clinical trials conducted in the 1990s and early 2000s confirmed that aspirin suppresses the recurrence of adenomatous polyps in people with a previous colon polyp. What's more, other limited epidemiologic data has shown that NSAID use may be associated with a lower incidence of or death from cancers at other sites, including the esophagus, stomach, breast, lung, prostate, urinary bladder and ovary.


Unfortunately, patients at high risk for cardiovascular disease have more serious cardiovascular events when taking NSAIDs and selective COX-2 inhibitors at high dosages for prolonged periods of time. On the other hand, some patients can tolerate these medications without cardiovascular complications quite well, especially at lower dosages when given once daily.


Further NSAID study needed

Scientists and clinicians are now working to determine how NSAIDs might protect against various cancers, possible effects of the long-term use of these drugs, optimum dosages and contraindications. They also are studying the benefits and risks of NSAID treatment across a broad range of treatment regimens, outcomes and patient populations.


Evidence from the nurses' study suggesting that aspirin use may be associated with a reduction in the recurrence of breast cancer may provide one more piece to this complicated puzzle. It certainly will launch the field further into this line of investigation.

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