Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial.

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.

[1]  L. Melvin,et al.  Effects of estrogen with and without progestin on urinary incontinence , 2005, Journal of Family Planning and Reproductive Health Care.

[2]  V. Fuster,et al.  Platelet-active drugs: the relationships among dose, effectiveness, and side effects. , 2004, Chest.

[3]  L. G. García Rodríguez,et al.  Risk of breast cancer among users of aspirin and other anti-inflammatory drugs , 2004, British Journal of Cancer.

[4]  Stuart J Pocock,et al.  Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study , 2004, BMJ : British Medical Journal.

[5]  R. McLeod,et al.  Nonsteroidal Anti-inflammatory Drugs and Aspirin for the Prevention of Colorectal Adenomas and Cancer: A Systematic Review , 2004, Diseases of the colon and rectum.

[6]  W. Willett,et al.  A Prospective Study of Aspirin Use and the Risk for Colorectal Adenoma , 2004, Annals of Internal Medicine.

[7]  R. López‐Ridaura,et al.  Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis , 2003, BMC Cancer.

[8]  E. Giovannucci,et al.  Aspirin use and lung cancer in men , 2003, British Journal of Cancer.

[9]  G. Anderson,et al.  Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative. , 2003, Cancer research.

[10]  J. Little,et al.  Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. , 2003, Gastroenterology.

[11]  P. Albert,et al.  Non-steroidal anti-inflammatory drug use is associated with reduction in recurrence of advanced and non-advanced colorectal adenomas (United States) , 2003, Cancer Causes & Control.

[12]  A. Neugut,et al.  Risk of lung carcinoma among users of nonsteroidal antiinflammatory drugs , 2003, Cancer.

[13]  Susan Halabi,et al.  A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. , 2003, The New England journal of medicine.

[14]  G. Beck,et al.  A randomized trial of aspirin to prevent colorectal adenomas. , 2003, The New England journal of medicine.

[15]  R. Shore,et al.  Aspirin and lung cancer in women , 2002, British Journal of Cancer.

[16]  Randall Harris,et al.  Chemoprevention of lung cancer by non-steroidal anti-inflammatory drugs among cigarette smokers. , 2002, Oncology reports.

[17]  K. Do,et al.  A Dose-finding Study of Aspirin for Chemoprevention Utilizing Rectal Mucosal Prostaglandin E2 Levels as a Biomarker , 2002 .

[18]  C. Rock,et al.  Colonic mucosal prostaglandin E2 and cyclooxygenase expression before and after low aspirin doses in subjects at high risk or at normal risk for colorectal cancer. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[19]  S. Khuder,et al.  Breast cancer and NSAID use: a meta-analysis , 2001, British Journal of Cancer.

[20]  L. G. García Rodríguez,et al.  Reduced Risk of Colorectal Cancer among Long-Term Users of Aspirin and Nonaspirin Nonsteroidal Antiinflammatory Drugs , 2001, Epidemiology.

[21]  M. Thun.  Beyond willow bark: aspirin in the prevention of chronic disease. , 2000, Epidemiology.

[22]  L. G. García Rodríguez,et al.  Reduced incidence of colorectal adenoma among long-term users of nonsteroidal antiinflammatory drugs: a pooled analysis of published studies and a new population-based study. , 2000, Epidemiology.

[23]  J. Manson,et al.  Self-selected posttrial aspirin use and subsequent cardiovascular disease and mortality in the physicians' health study. , 2000, Archives of internal medicine.

[24]  J. Manson,et al.  β-Carotene Supplementation and Incidence of Cancer and Cardiovascular Disease: the Women's Health Study. , 1999, Journal of the National Cancer Institute.

[25]  M. Taketo.  Cyclooxygenase-2 inhibitors in tumorigenesis (Part II). , 1998, Journal of the National Cancer Institute.

[26]  J. Manson,et al.  Aspirin Use and Colorectal Cancer: Post-Trial Follow-up Data from the Physicians' Health Study , 1998, Annals of Internal Medicine.

[27]  D. Scollard,et al.  Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. , 1998, Journal of the National Cancer Institute.

[28]  P. Ridker,et al.  Anti-Platelet Effects of 100 mg Alternate Day Oral Aspirin: A Randomized, Double-Blind, Placebo-Controlled Trial of Regular and Enteric Coated Formulations in Men and Women , 1996, Journal of cardiovascular risk.

[29]  W C Willett,et al.  Aspirin and the risk of colorectal cancer in women. , 1995, The New England journal of medicine.

[30]  E. Rimm,et al.  Aspirin Use and the Risk for Colorectal Cancer and Adenoma in Male Health Professionals , 1994, Annals of Internal Medicine.

[31]  R. Everson,et al.  Aspirin Use and Lung, Colon, and Breast Cancer Incidence in a Prospective Study , 1994, Epidemiology.

[32]  J. Manson,et al.  Low-dose aspirin and incidence of colorectal tumors in a randomized trial. , 1993, Journal of the National Cancer Institute.

[33]  A. Paganini-Hill,et al.  Aspirin use and chronic diseases: a cohort study of the elderly. , 1989, BMJ.

[34]  R. Doll,et al.  Randomised trial of prophylactic daily aspirin in British male doctors , 1988, British medical journal.

[35]  J. Baron.  Epidemiology of non-steroidal anti-inflammatory drugs and cancer. , 2003, Progress in experimental tumor research.

[36]  N. Cook,et al.  Baseline characteristics of participants in the Women's Health Study. , 2000, Journal of women's health & gender-based medicine.

[37]  David R. Cox,et al.  Regression models and life tables (with discussion , 1972 .

[38]  R. Muir,et al.  Muir's textbook of pathology , 1971 .