title: Lack of effect of celecoxib on prostaglandin E2 concentrations in nipple aspirate fluid from women at increased risk of breast cancer.
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 E(2) (PGE(2)) has tumor growth-promoting activity. The COX-2 isoform is the primary enzyme involved in PGE(2) production in cancerous tissue.
  
  
  OBJECTIVE
  We administered the COX-2 inhibitor celecoxib (200 mg b.i.d.) to women at increased breast cancer risk. Our hypothesis was that PGE(2) 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 PGE(2) levels in NAF (reflecting a decreased breast tissue eicosanoid production) and plasma.
  
  
  OBJECTIVE
  To determine if PGE(2) 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).
  
  
  METHODS
  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
  PGE(2) concentrations in NAF and plasma were detectable in samples using two measurement techniques. On average, NAF PGE(2) levels were 81-fold higher in NAF than in matched plasma. Technically, there were differences in PGE(2) concentrations measured in similar fluids depending on the assay technique used (RIA versus chemiluminescence immunoassay). There were no significant decreases in PGE(2) concentrations after celecoxib administration.
  
  
  CONCLUSIONS
  PGE(2) can be measured in NAF. PGE(2) levels are concentrated in NAF when compared with matched plasma samples. Celecoxib 200 mg b.i.d. does not appear to significantly decrease PGE(2) concentrations in NAF and plasma.
authors.affiliation: Department of Surgery, University of Missouri-Columbia, One Hospital Drive, Room M588, Columbia, MO 65212, USA. sautere@health.missouri.edu
authors.forename: Edward R
authors.initials: ER
authors.lastname: Sauter
authors.forename: Lisa
authors.initials: L
authors.lastname: Schlatter
authors.forename: John
authors.initials: J
authors.lastname: Hewett
authors.forename: Debra
authors.initials: D
authors.lastname: Koivunen
authors.forename: John T
authors.initials: JT
authors.lastname: Flynn
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001943:Breast Neoplasms / Q000209:etiology / Q000517:prevention & control*; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009558:Nipples / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D012307:Risk Factors; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D015232:Dinoprostone