Aspirin May Lower Cancer Risk, but Jury Is Still Out

Roxanne Nelson

March 30, 2009

March 30, 2009 — A growing body evidence suggests that aspirin-related nonsteroidal anti-inflammatory drugs (NSAIDs) might exert a chemopreventive effect, particularly for colorectal cancers.

However, because of ethical constraints, there are no long-term randomized placebo-controlled clinical trials on aspirin use and prevention of cancer, note the authors of a review paper published online March 26 in the Lancet. Although opportunistic trials of aspirin that were designed to test vascular protection provide some evidence of a reduction in cancer, more evidence from other sources is needed before the role for aspirin in chemoprevention can be better defined.

"The use of aspirin in relation to a vascular event is virtually proven," said coauthor Alison M. Gallagher, RPHNutr, DPhil, senior lecturer in biomedical sciences at the University of Ulster, in Northern Ireland, United Kingdom. "In addition, with respect to cancer, the evidence is as yet inconclusive but is, in my opinion, highly persuasive."

"The evidence for aspirin in colorectal cancer is very persuasive and there is some evidence for similar beneficial effects on other cancers, although the evidence overall for other cancer sites is less consistent," she told Medscape Oncology.

The evidence for aspirin in colorectal cancer is very persuasive.

The benefits of aspirin in vascular disease have been well documented, but the most conclusive evidence for an association between aspirin and cancer would have to be demonstrated by randomized controlled trials. However, because the risks for both vascular events and cancer increase with age, the denial of vascular benefits to individuals in the control group of a chemoprevention trial would probably be judged unethical, write the authors.

Because aspirin use is also associated with a risk for gastric bleeding, a safer form of aspirin needs to be developed to improve the risk–benefit balance, they note.

"Aspirin certainly benefits conditions other than cancer (namely, vascular health) and this should be taken into account when deciding whether it should be part of any prophylactic treatment for high-risk patients," said Dr. Gallagher. "Indeed, we would argue that the benefit of a reduced risk of heart attack and stroke largely outweighs the increased risk of gastric bleed associated with aspirin use."

Randomized Trials and Cancer Prevention

Dr. Gallagher and colleagues summarized the evidence in published studies supporting the potential benefit of aspirin and natural salicylates in cancer prevention.

Data from 3 large randomized trials, designed to examine the effect of aspirin on vascular disease, showed varying results. In the Physicians' Health Study, which included 22,071 American men randomized to 325 mg aspirin or placebo every other day, the relative risk of developing colorectal cancer in the aspirin group, compared with the placebo group, at 5 years was 1.15 (95% confidence interval, 0.80–1.65), they noted.

A British study of 5000 male doctors showed that after 6 years, cancer deaths were 18% lower in the aspirin-treated group (500 mg daily), but there was no effect on nonfatal cancer incidence. The Women's Health Study examined 40,000 American women randomized to 100 mg aspirin or placebo every other day. At 10 years, aspirin users did not show a reduction in total cancer, breast cancer, or colon cancer incidence. The researchers note, however, that deaths from lung cancer were reduced among aspirin users in all 3 trials (by 22%, 36%, and 18%, respectively).

They also point to the fact that aspirin effects on cancer were not the primary end point in any of these studies, and therefore all had limitations.

Observational Studies

Published data are extensive on the use of aspirin and NSAIDs to reduce the incidence of recurrent rectal and colonic polyps, which are the precursor to most colorectal cancers. Several observational studies have shown a reduction in both polyp number and growth, but the effects cease once the NSAID is no longer given, the authors write, and "overviews of observational studies have suggested relative risks attributable to aspirin of 0.71."

The ongoing Nurses' Health Study, with a cohort of almost 80,000 American women, showed a 12% reduction in cancer deaths with aspirin use, which became statistically significant at 10 years and increased to 44% by 20 years. Although only a modest association with death from all cancers was observed (relative risk [RR], 0.88), it was statistically significant for death from colorectal cancer (RR, 0.72) (Arch Intern Med. 2007;167:562-572).

Aspirin use has also been associated with a reduced risk for other types of malignancies, but study results have been less consistent than in the colorectal studies, according to the authors. For example, the large Cancer Prevention Study II showed a significant reduction in overall cancer for men only, a reduction in colon and prostate cancer, and a nonsignificant reduction in breast cancer. In addition, 20 observational studies found that NSAIDs appear to offer a degree of protection against breast cancer and might be of benefit to women with cancer; some benefit has also been observed for both gastric and esophageal cancers.

No Consensus on Dose or Usage

The dose and duration of aspirin use needed to exert a protective effect are not known, the authors note. Although 2 studies have suggested that 81 mg daily is effective, others have used doses of 300 mg or more. A number of trials have suggested that the duration and continuity of use is important to achieve and maintain a protective effect.

The authors also point out that there are differing viewpoints within the medical community as to whether or not patients at a high risk for cancer should be advised to use prophylactic aspirin.

Based on current epidemiologic and clinical evidence, some physicians feel that "there is little doubt that aspirin and related compounds have considerable potential as chemopreventive agents for colorectal cancer." Conversely, others believe that "in view of the adverse effects of NSAIDs and uncertainties about dose and duration of use, to recommend their use as standard medical practice for cancer prevention would be premature."

We feel that the patient's own values and assessment of the risks and benefits are of major importance and, ideally, he or she should decide about aspirin prophylaxis.

"At present, I am not aware of aspirin being routinely recommended for reducing colorectal cancer in high-risk individuals," said Dr. Gallagher. "However, our feeling, on the basis of available evidence, is that for older people and those at increased risk of cancer, aspirin should be considered.

"Given the proven vascular benefits and highly promising anticarcinogenic effects, we feel that the patient's own values and assessment of the risks and benefits are of major importance and, ideally, he or she should decide about aspirin prophylaxis," she added.

Funding source is not indicated in the paper. The researchers have disclosed no relevant financial relationships.

Lancet. Published online before print March 27, 2009.

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