May 25, 2004 — Aspirin use is associated with reduced risk of breast cancer, according to the results of a population-based, case-controlled trial published in the May 26 issue of The Journal of the American Medical Association. The investigators and editorialist suggest that prospective trials are needed to definitively prove the association.

"While cancer epidemiology and prevention have traditionally focused on the identification and modification of lifestyle factors that may increase or decrease the risk of various cancers, much recent attention has been centered on chemoprevention, the use of chemical agents to prevent or inhibit the carcinogenic process," write Mary Beth Terry, PhD, from Columbia University in New York City, and colleagues. "Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with a decrease in the risk of several cancers, including breast cancer. Given the importance of estrogen in the pathogenesis of breast cancer, the ability of aspirin and other NSAIDs to protect against breast cancer could vary according to hormone receptor status."

From 1996 to 1997, the investigators conducted in-person interviews with 1,442 breast cancer patients and 1,420 controls. Ever use of aspirin or other NSAIDs at least once per week for at least six months was reported in 301 breast cancer patients (20.9%) and in 345 control patients (24.3%), with a 20% lower risk of breast cancer for ever use vs. nonusers (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.66 - 0.97)

Users of seven or more tablets per week had a risk reduction of 28% (OR, 0.72; 95% CI, 0.58 -0.90). The inverse association for ibuprofen was somewhat weaker (22% lower risk for less than three tablets per week vs. 8% lower risk for at least three tablets per week. Use of acetaminophen, which does not inhibit prostaglandin synthesis, was not associated with reduced incidence of breast cancer.

Aspirin use was associated with a 26% reduced risk in women with hormone receptor–positive tumors, but no risk reduction was oberved for women with hormone receptor–negative tumors.

"Our data, supported by other epidemiologic and laboratory evidence, bolster the case for the use of aspirin and NSAIDs as chemopreventive agents against breast cancer, particularly among postmenopausal women," the authors write. "The mechanisms are probably distinct from those that are protective against gastrointestinal tract cancers."

Study limitations include lack of data concerning the dose of the aspirin tablets, retrospective reporting of medication use, and potential confounding by a number of clinical variables. The authors recommend further studies to clarify the mechanisms underlying the protective effect of NSAIDs.

"There are many attractive features to such a chemopreventive agent, including its ease of use and association with reducing risk of other health outcomes," the authors conclude. "The potential benefits need to be balanced against potential harmful effects of long-term aspirin use such as peptic ulcer disease and gastrointestinal bleeding."

The National Cancer Institute and the National Institute of Environmental Health Sciences helped support this study.

In an accompanying editorial, Raymond N. DuBois, MD, PhD, from Vanderbilt University Medical Center in Nashville, Tennessee, recommends additional research before clinicians can make any definite recommendations to patients at risk for breast cancer.

"Despite the longstanding and ubiquitous nature of aspirin use, researchers are still exploring the clinical outcome of aspirin treatment in humans," he writes. "Women who take daily aspirin for cardiovascular indications may gain additional benefits with regard to reduction in their risk for certain cancers, such as hormone receptor–positive breast cancer. However, the optimal aspirin dose or regimen required to achieve a maximal reduction in cancer risk remains unknown."

JAMA. 2004;291:2433-2440, 2488-2489

Reviewed by Gary D. Vogin, MD