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The Women’s Health Study: A Randomized Controlled Trial

Nancy R. Cook, ScD; I-Min Lee, MBBS, ScD; J. Michael Gaziano, MD; David Gordon, MA; Paul M Ridker, MD; JoAnn E. Manson, MD, DrPH; Charles H. Hennekens, MD, DrPH; Julie E. Buring, ScD

JAMA. 2005;294:47-55.

Context  Basic research and observational evidence as well as results from trials of colon polyp recurrence suggest a role for aspirin in the chemoprevention of cancer.

Objective  To examine the effect of aspirin on the risk of cancer among healthy women.

Design, Setting, and Participants  In the Women’s Health Study, a randomized 2 x 2 factorial trial of aspirin and vitamin E conducted between September 1992 and March 2004, 39 876 US women aged at least 45 years and initially without previous history of cancer, cardiovascular disease, or other major chronic illness were randomly assigned to receive either aspirin or aspirin placebo and followed up for an average of 10.1 years.

Intervention  A dose of 100 mg of aspirin (n=19 934) or aspirin placebo (n=19 942) administered every other day.

Main Outcome Measures  Confirmed newly diagnosed invasive cancer at any site, except for nonmelanoma skin cancer. Incidence of breast, colorectal, and lung cancer were secondary end points.

Results  No effect of aspirin was observed on total cancer (n = 2865; relative risk [RR], 1.01; 95% confidence interval [CI], 0.94-1.08; P = .87), breast cancer (n = 1230; RR, 0.98; 95% CI, 0.87-1.09; P = .68), colorectal cancer (n = 269; RR, 0.97; 95% CI, 0.77-1.24; P = .83), or cancer of any other site, with the exception of lung cancer for which there was a trend toward reduction in risk (n = 205; RR, 0.78; 95% CI, 0.59-1.03; P = .08). There was also no reduction in cancer mortality either overall (n = 583; RR, 0.95; 95% CI, 0.81-1.11; P = .51) or by site, except for lung cancer mortality (n = 140; RR, 0.70; 95% CI, 0.50-0.99; P = .04). No evidence of differential effects of aspirin by follow-up time or interaction with vitamin E was found.

Conclusions  Results from this large-scale, long-term trial suggest that alternate day use of low-dose aspirin (100 mg) for an average 10 years of treatment does not lower risk of total, breast, colorectal, or other site-specific cancers. A protective effect on lung cancer or a benefit of higher doses of aspirin cannot be ruled out.

Author Affiliations: Divisions of Preventive Medicine (Drs Cook, Lee, Gaziano, Ridker, Manson, and Buring, and Mr Gordon), Cardiovascular Medicine (Drs Gaziano and Ridker), and Aging (Drs Gaziano and Buring), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Department of Epidemiology, Harvard School of Public Health, Boston (Drs Cook, Lee, Ridker, Manson, and Buring); Veterans Affairs Boston Healthcare System (Dr Gaziano); Department of Ambulatory Care and Prevention, Harvard Medical School, Boston (Dr Buring); and the Departments of Medicine and Epidemiology and Public Health, University of Miami School of Medicine, Miami, Fla, and Department of Biomedical Science, Center of Excellence, Florida Atlantic University, Boca Raton (Dr Hennekens).

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