Data from the US Women’s Health Study, which enrolled nearly 40,000 healthy women, indicate there is no benefit from either low-dose aspirin or vitamin E in prevention of cancer, according to two articles in the July 6 issue of the Journal of the American Medical Association.

A growing body of literature has supported a protective effect of aspirin and other nonsteroidal anti-inflammatory drugs on development of certain cancers, according to background information in the first article. Observational epidemiological investigations suggest a strong inverse association, with risk reductions as high as 20 percent to 50 percent for various cancer sites.

In contrast with the observational evidence on cancer incidence, data from randomized trials have been far more limited. The Physicians’ Health Study found no effect on colorectal cancer of 325 mg aspirin given every other day over a 5-year randomized period or in post-trial follow-up. In addition, no randomized trial has yet assessed the impact of aspirin on development of breast cancer.

The Women’s Health Study was a randomized, double-blind, placebo-controlled trial conducted between September 1992 and March 2004, which evaluated the balance of benefits and risks of 100 mg of aspirin every other day, and 600 IU of vitamin E every other day, on primary prevention of cardiovascular disease and cancer in a cohort of 39,876 healthy female health care professionals (average duration of follow-up, 10.1 years.)

In the first article, Nancy R. Cook, ScD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues evaluated the findings for aspirin with regard to cancer risk. In this part of the study, 19,934 women received a dose of 100 mg of aspirin every other day and 19,942 women received placebo.

The researchers found that aspirin had no observed effect on total cancer, breast cancer, colorectal cancer, or cancer of any other site, with the exception of lung cancer for which there was a trend toward reduction in risk (22 percent reduced risk). There was also no reduction in cancer death either overall or by site, except for lung cancer death (30 percent reduced risk). No evidence of differential effects of aspirin by follow-up time or interaction with vitamin E was found.

“The findings from the Women’s Health Study suggest that aspirin at a dose of 100 mg every other day is not effective in reducing risk of cancer in healthy women, although a beneficial effect on lung cancer cannot be ruled out. This large study of almost 40,000 women had a duration of 10 years of treatment and follow-up, which was the longest of any trial completed to date, and should be sufficient to detect long-term effects. To determine whether higher doses of aspirin taken daily would be effective in cancer prevention requires direct randomized trial data. Such data would need to be considered in the context of risk of gastrointestinal adverse effects before recommending higher-dose aspirin for cancer chemoprevention among low-risk individuals,” the authors concluded.

Low-Dose Aspirin and Vitamin E - Challenges and Opportunities in Cancer Prevention

In an accompanying editorial, Eric J. Jacobs, PhD, and Michael J. Thun, MD, of the American Cancer Society, Atlanta, commented on the findings by Cook et al.

“Should the null results with respect to cancer from this large, well-conducted, long-term randomized trial, or from other chemoprevention trials, be considered discouraging news for cancer chemoprevention in general- There have been some successes in cancer chemoprevention, such as the use of tamoxifen to prevent breast cancer in high-risk women. However, currently, no agent has been shown to do for cancer what statins do for cardiovascular disease, namely substantially and relatively safely reduce disease occurrence in individuals not at especially high risk.”

“Pharmacological primary prevention of diseases as heterogeneous as cancer is inherently difficult. Randomized trials of cancer chemoprevention will undoubtedly produce many null results. Nevertheless, continued systematic research on cancer chemoprevention, including long-term randomized trials of carefully chosen agents, is essential given the large potential benefits. At the same time, it is unrealistic to expect the discovery of an agent that will produce substantial reductions in overall cancer rates in the immediate future,” authors wrote.