SANTIAGO de COMPOSTELA, Spain—Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of breast cancer, finds a meta-analysis of 38 studies in the Journal of the National Cancer Institute.¹ October is National Breast Cancer Awareness Month and risk reduction strategies are a key part of the current agenda.

"The results are encouraging and may help us better understand the importance of role of inflammation in the pathology of the disease," said Mahyar Etminan, MD, in a press release. Dr. Etminan is an assistant professor of medicine at the University of British Columbia, and member of the Vancouver Coastal Health Research Institute in Canada.

Chronic inflammation is associated with several cancers, "[h]owever, we don't recommend the routine use of NSAIDs for breast cancer prevention until large randomized trials confirm these findings." Results from an ongoing prevention trial will be available in 2009.

Breast cancer risk 12% in NSAID users, 13% lower in aspirin users

The new meta-analysis included 16 case-control studies, 18 cohort studies, 3 case-control studies nested in well-defined cohorts, and 1 clinical trial. There were >2.7 million women included in the trials.

Regular use of NSAIDs was associated with a 12% relative risk reduction in breast cancer, compared with nonusers. A separate analysis for aspirin found a 13% relative risk reduction in breast cancer; another found a 21% relative risk reduction for ibuprofen. There was no evidence of a dose-response relationship, the study showed. Some studies in the meta-analysis showed that coxibs may also protect against breast cancer.

The new study does have some limitations, the authors point out. For example, some of the studies used in the meta-analysis may have been subject to recall bias. Moreover, the studies did not adjust for behaviors associated with NSAID use, which may be associated with a reduced risk of breast cancer.

In an accompanying editorial,² Louise R. Howe, PhD, of Weill Cornell Medical College in New York, NY and Scott M. Lippman, MD of the University of Texas M.D. Anderson Cancer Center in Houston, write that the new findings “support targeting COX/prostaglandin signaling axis to prevent breast cancer. The cardiovascular side effects associated with coxibs and potentially other NSAIDs necessitate refocusing COX-directed cancer prevention strategies to avoid this danger.”

The future may be personalized use of NSAIDs for breast cancer reduction

“Responsiveness to an individual NSAID may be predicated on hormone receptor expression, menopausal status and hormone replacement therapy use, or HER2 status (a routinely examined clinical marker that may be a surrogate for COX-2 over suppression on the breast),” they write. Risk-modeling and elucidating the contribution of variant alleles “will advance us toward personalized use of NSAIDs for reducing breast cancer risk.”

References

1. Takkouche B, Regueira-Méndez C, Etminan M. Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta analysis. J Natl Cancer Inst. 2008;100:1-9.
2. Howe LR, Lippman SM. Modulation of breast cancer risk by nonsteroidal anti-inflammatory drugs. J Natl Cancer Inst. 2008;100:1420-1423.