Lack of Effect of Celecoxib on Prostaglandin E2 Concentrations in Nipple Aspirate Fluid from Women at Increased Risk of Breast Cancer

Abstract

Abstract Background: Cyclooxygenase enzymes (COX-1, COX-2, and COX-3) convert arachidonic acid to prostaglandins, prostacyclins, thromboxanes, and other hydroxy fatty acids. Among these, prostaglandin E2 (PGE2) has tumor growth-promoting activity. The COX-2 isoform is the primary enzyme involved in PGE2 production in cancerous tissue. Objective/Hypothesis: We administered the COX-2 inhibitor celecoxib (200 mg b.i.d.) to women at increased breast cancer risk. Our hypothesis was that PGE2 would be secreted in breast nipple aspirate fluid (NAF), that levels in NAF would be higher than in corresponding plasma, and that celecoxib would decrease PGE2 levels in NAF (reflecting a decreased breast tissue eicosanoid production) and plasma. Specific Aim: To determine if PGE2 concentrations in NAF and plasma decrease after a 2-week course of celecoxib and then return to baseline 2 weeks after stopping the medication (washout). Study Design: NAF and plasma were collected before celecoxib treatment, 2 weeks after taking celecoxib, and 2 weeks after washout. Each woman served as her own control. Results: PGE2 concentrations in NAF and plasma were detectable in samples using two measurement techniques. On average, NAF PGE2 levels were 81-fold higher in NAF than in matched plasma. Technically, there were differences in PGE2 concentrations measured in similar fluids depending on the assay technique used (RIA versus chemiluminescence immunoassay). There were no significant decreases in PGE2 concentrations after celecoxib administration. Conclusions: PGE2 can be measured in NAF. PGE2 levels are concentrated in NAF when compared with matched plasma samples. Celecoxib 200 mg b.i.d. does not appear to significantly decrease PGE2 concentrations in NAF and plasma.