Alternate-Day, Low-Dose Aspirin and Cancer Risk: Long-Term Observational Follow-up of a Randomized Trial

Abstract

Background Observational studies and meta-analyses of trials suggest daily aspirin use may affect cancer risk, particularly for colorectal cancer, but evidence regarding alternate-day use is scant. Objective To examine the association between long-term use of alternate-day low-dose aspirin and cancer incidence in healthy women. Design Observational follow-up of a randomized controlled trial. Setting U.S. female health professionals. Participants 39,876 women aged 45 and over in the Women’s Health Study, 33,682 of whom continued observational follow-up. Intervention 100 mg of aspirin or placebo administered every other day until March 2004, with a median 10-year follow-up. Post-trial observational follow-up continued through March 2012. Measurements Incidence of cancer. Results 5,071 cancers were confirmed throughout follow-up, including 2,070 breast, 451 colorectal, 431 lung cancers, and 1,391 cancer deaths. Over the entire follow-up there was no overall effect of aspirin on total (hazard ratio (HR) = 0.97, 95% confidence interval (CI) = 0.92-1.03, p=0.31), breast (HR=0.98, 95% CI = 0.90-1.07 p=0.65) or lung (HR=1.04, 95% CI = 0.86-1.26, p=0.67) cancer. Incidence of colorectal cancer was lower in the aspirin group (HR=0.80, 95% CI = 0.67-0.97, p=0.021), primarily due to a reduction in proximal colon cancer (HR=0.73, 95% CI = 0.55-0.95, p=0.022), with the effect emerging after 10 years. The post-trial reduction in colorectal cancer was 42% (HR=0.58, 95% CI = 0.42-0.80, p<0.001). There was no extended effect on cancer deaths or colorectal polyps. There were more reported gastrointestinal bleeds (HR=1.14, 95% CI=1.06-1.22, p<0.001) and peptic ulcers (HR=1.17, 95% CI=1.09-1.27, p<0.001) in the aspirin group. Limitations Data were available only for women. Not all women received extended follow-up, and the possibility of ascertainment bias post-trial cannot be ruled out. Gastrointestinal bleeding, peptic ulcer, and polyp information was obtained only from self-report during extended follow-up. Conclusions Long-term use of alternate-day, low-dose aspirin may reduce risk for colorectal cancer in healthy women.

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