Selective cyclooxygenase-2 (COX-2) inhibitors and breast cancer risk

Background: Recent epidemiologic and laboratory studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of breast cancer through inhibition of cyclooxygenase-2 (COX-2). Methods: We conducted a case-control study to measure the association between selective cox-2 inhibitors, particularly celecoxib, rofecoxib, valdecoxib and non-specific NSAID subgroups, and breast cancer risk. Between 2003 and 2006, a total of 18,368 incident breast cancer cases were identified in the Ingenix/Lab Rx insurance database, which contains clinical encounter and drug prescription data. Four controls per case were randomly selected, matched on age and time in database. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: Breast cancer risk was inversely associated with both non-specific NSAID and selective COX-2 inhibitor use. Greater than 12 months' duration of use of Celecoxib at a standard dose (200. mg/day) was associated with a 16% decrease in breast cancer risk (OR = 0.84, 95% CI = 0.73, 0.97). We observed the greatest risk reduction in association with >2 years of rofecoxib exposure (OR = 0.54, 95% CI = 0.37, 0.80). Acetaminophen, a compound with less biological plausibility for chemoprevention, showed no significant association with the risk of developing breast cancer. Conclusion: Consistent with animal models and laboratory investigations, higher doses of selective COX-2 inhibitors were more protective against breast cancer than non-specific NSAIDs. With exposure to rofecoxib, a selective COX-2 inhibitor, breast cancer risk reduction was appreciable (46%), suggesting a possible role for selective COX-2 inhibitors in breast cancer prophylaxis.