Aspirin May Lower Cancer Risk, but

Jury Is Still Out

Roxanne Nelson

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.

Related Links

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Aspirin Chemoprevention in Patients With Increased Risk for Colorectal Cancer: A

Cost-effectiveness Analysis
Aspirin or NSAIDs for the Primary Prevention of Colorectal Cancer
NSAIDs and Breast Cancer: A Possible Prevention and Treatment Strategy
Nonsteroidal Antiinflammatory Drugs and Breast Cancer Risk: The Multiethnic
Cohort
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Roxanne Nelson is a freelance journalist for Medscape Oncology.

Medscape Medical News 2009. © 2009 Medscape