The impact of nonsteroidal anti-inflammatory drugs on endocrine therapy outcomes in breast cancer patients



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Obesity is a known risk factor for postmenopausal breast cancer, and is associated with worse disease prognosis in pre- and postmenopausal women. Adjuvant hormonal therapies improve disease prognosis in obese women, but many still recur. Given that obesity induces inflammation and increases levels of cyclooxygenase-2 (COX-2) enzyme, resulting in tumor proliferation, this retrospective study investigated if women on anti-inflammatory drugs would have improved disease outcomes by reduced production of prostaglandins by COX-2 pathway. Four hundred and forty women treated for invasive breast cancer in San Antonio clinics were included. Cases were classified as NSAID users if notes included daily use of aspirin, ibuprofen, celecoxib or another COX-2 inhibitor; patients were categorized as NSAID nonusers if they were not taking any NSAIDs, or if they used COX-2 drugs for pain as needed rather than daily. Patients on NSAIDs were more likely to be older, be slightly more obese and postmenopausal. NSAID and NSAID nonusers did not statistically significantly differ in regards to BMI categories, tumor stage, hormone receptor status, type of invasive tumor, ethnicity/race and type of surgery. NSAID users had significantly less recurrence rates compared to nonusers (p=0.05). Further, time to disease progression was delayed by almost 28 months in patients who were NSAIDs users. Although this trend was non-significant statistically due to low number of total recurrences, it is promising in the clinical setting. In a logistic regression model using NSAID use, BMI categories and hormonal therapy drug as independent variables to predict recurrence, use of NSAID was only statistically significant in the univariate model. Overweight women were more likely to develop recurrence than normal weight when holding NSAID use and endocrine therapy constant. Obese women had increase recurrence risk, but the trend was not statistically significant. Females using aromatase inhibitors were less likely to recur than those on tamoxifen. The results of this exploratory study had limited power to determine multiple modulating factors, but because they suggest a major clinical benefit, further analyses in a larger sample size are needed to confirm these findings.