Aspirin May Reduce Breast Cancer Metastasis and Mortality Rates

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New data suggest that women who take aspirin regularly following a breast cancer diagnosis cut their risk of death and distant metastases by nearly 50%. The prospective observational Nurses’ Health Study (NHS) was conducted in collaboration by researchers from Brigham and Women’s Hospital (BWH), Dana-Farber Cancer Institute, and Harvard Medical School. The investigators said they found no preventative correlation between aspirin use and breast cancer incidence and cautioned that further research is needed before physicians recommend women with breast cancer take aspirin.

The ongoing NHS is designed to examine how lifestyle factors affect women’s health. For this analysis, investigators looked at data for a subset of 4164 women who are registered nurses and received a diagnosis of stage I, II, or III breast cancer between 1976 and 2002. The women were followed until June 2006, and during this period, there were 732 deaths, of which 341 were from breast cancer. Overall, there were 400 distant recurrences.

Starting in 1980, frequency of aspirin use was assessed every 2 years via a self-reported questionnaire. Usage categories included never, past, and current, and options for frequency of aspirin use included 1 day per week, 2 to 5 days per week, and 6 to 7 days per week. Women who never provided an aspirin assessment after diagnosis or for whom no baseline assessment was available were excluded from the analyses.

Most women (35%) who reported taking aspirin regularly did so to prevent heart disease. The exact dosage was not recorded, but the investigators said the typical dose used for heart disease prevention is ~81 mg per day. Other more commonly reported reasons included muscle or joint pain (16%), headache (13%), backache (7%), and menstrual cramps (1%).

The primary endpoints of the analyses included death from breast cancer, distant recurrence, and death from any cause. The study authors said aspirin use was associated with a reduced risk of death relative to never-aspirin users. Adjusted relative risk (RR) for 1 day of aspirin use per week compared with no use was 1.07 (95% CI, 0.70-1.63); for 2 to 5 days of use per week, RR was 0.29 (95% CI, 0.16- 0.52), and for 6 to 7 days of aspirin use per week, RR was 0.36 (95% CI, 0.24-0.54). Metastasis results were similar, with an adjusted RR of 0.91 (95% CI, 0.62-1.33) for 1 day of use compared to none; 0.40 (95% CI, 0.24-0.65) for 2 to 5 days of use; and 0.57 (95% CI, 0.39-0.82; test for trend, P = .03) for 6 to 7 days of aspirin use. When adjusting the analyses for variables associated with an increased risk of breast cancer death, such as stage, menopausal status, body mass index, and estrogen receptor status, results were similar.

NHS found no association between aspirin use and breast cancer incidence. In addition, women who had used aspirin for at least 5 years had a modest reduction in the risk of death from breast cancer. The investigators also looked for any relationship between breast cancer survival and distant metastasis with nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and found indications of a protective effect from NSAIDs but none from acetaminophen.

Previous studies of the effect of aspirin and other NSAIDs on breast cancer survival rates and metastasis have produced mixed results. Although this inherently limited observational study did not conclusively determine the mechanism of aspirin’s action, investigators said one possible explanation for the risk reduction is that by inhibiting the enzyme cyclooxygenase, NSAIDs may suppress estrogen synthesis, thereby stunting breast cancer proliferation. Unique among NSAIDs, aspirin irreversibly inhibits cyclooxygenase. Another theory maintains aspirin’s anti-inflammatory effects may inhibit cancer growth.

“More research is needed to determine how aspirin, which is an NSAID, may work to prohibit the recurrence of breast cancer,” said Michelle Holmes, MD, DrPH, lead author of the paper and a researcher and associate professor of medicine at the Channing Laboratory at BWH, in a BWH press release.

The study’s authors urge women with breast cancer to discuss the risks and benefits of regular aspirin use with their physician before starting an aspirin regimen. Aspirin is known to interact with other medications, and it is associated with adverse effects, including gastrointestinal bleeding. They noted, however, that “aspirin has relatively benign adverse effects compared with cancer chemotherapeutic drugs and may also prevent colon cancer, cardiovascular disease, and stroke” and said it appears to affect estrogen receptor—positive and –negative tumors.

Journal of Clinical Oncology

The investigators said further studies, possibly including a randomized trial of aspirin use after breast cancer diagnosis, were needed to confirm their findings and establish aspirin’s mechanism of action in breast cancer. Still, they remained optimistic about the study’s findings. “The ability to affect length and quality of life after breast cancer by a common medication would be welcome,” they wrote, concluding, “If confirmed, our results may broaden the scope of interventions available to reduce breast cancer—related morbidity and mortality.” The article was published online ahead of print in the .