Aspirin Benefit Seen in Established Breast Cancer

Chalk up another use for aspirin: The drug appears to substantially reduce breast cancer survivors' risk of metastasis and death, researchers found.

An aspirin at least two days a week significantly reduced breast cancer death risk by 64% to 71%, Michelle D. Holmes, MD, DrPH, of the Channing Laboratory at Harvard and Brigham and Women's Hospital in Boston, and colleagues reported online in the Journal of Clinical Oncology.

The risk reduction for distant metastasis in breast cancer survivors taking aspirin at least two days a week was a significant 43% to 60% in the analysis of the Nurses' Health Study data through 2006.

This cut the risk of death from any cause nearly in half, Holmes' group noted.

These results could have "considerable clinical importance," they wrote, given the drug's relatively benign adverse effects compared with cancer chemotherapy agents as well as its other benefits in preventing colon cancer, cardiovascular disease, and stroke.

These findings were "all the more notable because the Nurses' Health Study did not find an association between aspirin use and breast cancer incidence," Holmes' group wrote.

Prevention of metastasis may be different, they said.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) nonselectively block Cox-2 overexpression, which has been linked to metastasis of breast cancer, and also lower serum estradiol.

The anti-inflammatory effect of aspirin might itself hold benefits against cancer, added Lori Pierce, MD, of the University of Michigan in Ann Arbor, who commented on behalf of the American Society of Clinical Oncology.

However, she cautioned that aspirin isn't risk-free, noting it can cause GI bleeding.

Nevertheless, "these are promising findings, and if they are confirmed in additional clinical trials, physicians may be able to regularly recommend aspirin to their breast cancer patients to reduce risk of cancer spread and mortality," she wrote in a prepared statement.

Further study is needed to determine the mechanism and also to prospectively confirm the benefit, the investigators agreed.

The analysis included responses from 4,164 female registered nurses diagnosed with early stage breast cancer between 1976 and 2002 with follow-up through death or June 2006.

Aspirin use assessments in the first year after diagnosis were excluded since the drug is discouraged during chemotherapy.

Among these women who survived for more than a year after diagnosis, those who used aspirin more were less likely to subsequently die from breast cancer (P<0.001 for trend).

Compared with women who never used aspirin, the multivariate adjusted relative risk of breast cancer death was:

• Similar for past users (RR 0.88, 95% confidence interval 0.64 to 1.22)
• Similar for those with current use one day a week (RR 1.07, 95% CI 0.70 to 1.63)
• Significantly lower for current two to five days-a week use (RR 0.29, 95% CI 0.16 to 0.52)
• Significantly lower for current use six or seven days a week (RR 0.36, 95% CI 0.24 to 0.54)

For distant recurrence risk, the results were much the same (P=0.03 for trend).

The multivariate adjusted metastasis risks compared with women who never used aspirin was not reduced significantly with past (RR 1.03) or current one day a week use (RR 0.91) but was with two to five (RR 0.40, 95% CI 0.24 to 0.65) and six to seven days a week use (RR 0.57, 95% CI 0.39 to 0.82).

For overall mortality, the results were just as good (P=0.004 for trend), with multivariate-adjusted risk reductions of 47% for two to five day a week use (RR 0.53, 95% CI 0.37 to 0.76) and 46% for daily or nearly daily use (RR 0.54, 95% CI 0.41 to 0.70).

However, this appeared to be accounted for by the reductions in breast cancer-related deaths, the researchers noted.

Despite low statistical power, they found a suggestion of a breast cancer survival advantage with other NSAIDs but not with acetaminophen (Tylenol).

"The lack of association with acetaminophen suggests that the associations seen with aspirin and NSAIDs may represent biologically plausible effects and not just confounding by indication," Holmes and colleagues wrote in the JCO paper.

They cautioned, though, that the study was limited by use of self-reporting for aspirin intake, treatment, and distant recurrence.

Nor did the study have any information on aspirin dose, although most regular use was likely for heart disease prevention at the 81 mg/day level, they suggested.

And, although most breast cancer patients live at least five years, the results may be generalizable only to longer-term breast cancer survivors, they added.

The study was supported by a grant from the National Institutes of Health.

The researchers reported no conflicts of interest.

Pierce provided no information on conflicts of interest.

Primary source: Journal of Clinical Oncology Source reference: Holmes MD, et al "Aspirin intake and survival after breast cancer" J Clin Oncol 2010; 28.