Current issues of ACP Journal Club are published in Annals of Internal Medicine


Low-dose aspirin did not prevent cancer in healthy women


ACP J Club. 2006 Jan-Feb;144:8. doi:10.7326/ACPJC-2006-144-1-008

Related Content in this Issue
• Companion Abstract and Commentary: Vitamin E did not prevent cardiovascular disease and cancer in healthy women

Clinical Impact Ratings

GIM/FP/GP: 6 stars

Hospitalists: 6 stars

Source Citation

Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294:47-55. [PubMed ID: 15998890]



In healthy women ≥ 45 years of age, how effective is aspirin in preventing cancer?


Design: Randomized placebo-controlled trial (Women's Health Study [WHS], a randomized 2 × 2 factorial trial).

Allocation: Concealed.*

Blinding: Blinded {participants, health care providers, data collectors, and outcome assessors}†.*

Follow-up period: Mean 10.1 years.

Setting: {A mail-based trial in female health care professionals in the United States}†.

Participants: 39 876 women ≥ 45 years of age (mean age 55 y) without a history of cancer (except nonmelanoma skin cancer), cardiovascular disease, or other major chronic illness and no history of adverse effects to aspirin who were not taking aspirin or nonsteroidal antiinflammatory drugs > once per week; anticoagulants or corticosteroids; or individual supplements of vitamin A, vitamin E, or β-carotene > once per week.

Intervention: Aspirin (100 mg every other d) (n = 19 934) or matching placebo (n = 19 942).

Outcomes: Total invasive cancer, excluding nonmelanoma skin cancer. Secondary outcomes were breast, colorectal, and lung cancer.

Patient follow-up: 97% for morbidity and 99% for mortality (intention-to-treat analysis).

Main results

Aspirin and placebo groups did not differ for incidence of total invasive cancer (Table). Groups also did not differ for incidence of breast, colorectal, or lung cancer (Table)or for total cancer mortality or site-specific cancer mortality, except for lung cancer mortality, which showed a reduction with aspirin (0.3% vs 0.4%; relative risk 0.70, 95% CI 0.50 to 0.99).


In healthy women ≥ 45 years of age, low-dose aspirin did not prevent total cancer or breast, colorectal, or other types of cancer.

*See Glossary.

†Information provided by author.

Sources of funding: National Heart, Lung, and Blood Institute and National Cancer Institute.

For correspondence: Dr. N.R. Cook, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. E-mail

Table. Aspirin vs placebo to prevent total invasive cancer and breast, colorectal, and lung cancer at mean 10.1 years‡

Outcomes Aspirin Placebo RRI (95% CI) NNH
Total invasive cancer 7.2% 7.2% 1.0% (−8 to 6) Not significant
Total cancer death 1.4% 1.5% 5.0% (−11 to 19) Not significant
Breast cancer 3.1% 3.1% 2.0% (−9 to 13) Not significant
Colorectal cancer 0.7% 0.7% 3.0% (−24 to 23) Not significant
Lung cancer 0.5% 0.6% 22% (−3 to 41) Not significant

‡Abbreviations defined in Glossary; RRI, RRR, NNH, NNT, and CI calculated from data in article.


2 studies by Cook and Lee and their colleagues complete the reporting of primary outcomes from the Women's Health Study, a trial of low-dose aspirin and high-dose α-tocopherol in the primary prevention of CVD and cancer in generally healthy female health care professionals. The 10-year results were fairly convincingly negative, with no hint of a benefit for either intervention in the primary endpoints. So many comparisons were made examining secondary outcomes and subgroups that caution is needed in interpreting any of these marginally significant findings, such as vitamin E reducing CV death or aspirin increasing cancer in never-smokers.

The question then becomes, to whom and to what interventions do these results apply? Although all healthy women in the health care professions > 45 years of age were eligible, only 10% of the participants were > 65 years. Thus, it may be hard to apply these results to older women. Subgroup analysis suggested a benefit in the older age group with both vitamin E and low-dose aspirin (1) in the prevention of CVD. Doses of aspirin higher than the 100 mg every other day that was tested in the study by Cook and colleagues might decrease the incidence of colorectal cancer (2, 3) but would be expected to carry greater toxicity. The finding that α-tocopherol supplements had no benefit or might even increase mortality (4) is at odds with well-established epidemiologic data regarding diets high in vitamin E, including α-tocopherol and other antioxidants. Postulated causes include the displacement of other antioxidants, such as γ-tocopherol by α-tocopherol supplements (5). The observational epidemiologic data also reflect uncontrolled confounding by other factors (e.g., healthy diet).

The bottom line for clinicians is that, for healthy women 45 to 64 years of age (who represented 90% of the participants in these 2 studies), there is no substantial benefit to long-term use of low-dose aspirin or high-dose vitamin E supplements. Studies specifically addressing these interventions in older women would be useful.

Laura Rees Willett, MD
Robert Wood Johnson Medical School
New Brunswick, New Jersey, USA


1. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352:1293-304. [PubMed ID: 15753114]

2. Asano TK, McLeod RS. Nonsteroidal anti-inflammatory drugs and aspirin for the prevention of colorectal adenomas and cancer: a systematic review. Dis Colon Rectum. 2004;47:665-73. [PubMed ID: 15054679]

3. Chan AT, Giovannucci EL, Meyerhardt JA, et al. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA. 2005;294:914-23. [PubMed ID: 16118381]

4. Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46. [PubMed ID: 15537682]

5. Huang HY, Appel LJ. Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr. 2003;133:3137-40. [PubMed ID: 14519797]