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

¹ Department of Surgery, University of Missouri-Columbia, Columbia, Missouri and ² Thomas Jefferson University, Philadelphia, Pennsylvania

Requests for reprints: Edward R. Sauter, Department of Surgery, University of Missouri-Columbia, One Hospital Drive, Room M588, Columbia, MO 65212. Phone: 573-882-4471; Fax: 573-884-4585. E-mail: sautere{at}health.missouri.edu

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.