Celecoxib concentration predicts decrease in prostaglandin E2 concentrations in nipple aspirate fluid from high risk women.
BACKGROUND
Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E2 concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE2 response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE2 concentrations from baseline to end of treatment, and 2) whether menopausal status influenced circulating levels of celecoxib.


METHODS
Matched NAF and plasma were collected from 46 high risk women who were administered celecoxib twice daily for two weeks, 20 subjects receiving 200 mg and 26 subjects 400 mg of the agent. NAF and plasma samples were collected before and 2 weeks after taking celecoxib.


RESULTS
In women taking 400 mg bid celecoxib, plasma concentrations of the agent correlated inversely with the change in NAF PGE2 levels from pre- to posttreatment. Nonsignificant trends toward higher celecoxib levels were observed in post- compared to premenopausal women. There was a significant decrease in NAF but not plasma PGE2 concentrations in postmenopausal women who took 400 mg celecoxib (p = 0.03).


CONCLUSIONS
In high risk women taking 400 mg celecoxib twice daily, plasma concentrations of celecoxib correlated with downregulation of PGE2 production by breast tissue. Strategies synergistic with celecoxib to downregulate PGE2 are of interest, in order to minimize the celecoxib dose required to have an effect.
Sauter
Edward R
ER
Department of Surgery, University of Missouri, Columbia, MO, USA. sautere@health.missouri.edu
Qin
Wenyi
W
Hewett
John E
JE
Ruhlen
Rachel L
RL
Flynn
John T
JT
Rottinghaus
George
G
Chen
Yin-Chieh
YC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001826:Body Fluids / Q000737:chemistry*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use; D015232:Dinoprostone / Q000032:analysis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008593:Menopause / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009558:Nipples / Q000378:metabolism*; D009994:Osmolar Concentration; D011379:Prognosis; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis* / Q000627:therapeutic use*; D012307:Risk Factors; D013048:Specimen Handling / Q000379:methods; D013396:Suction; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis* / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D015232:Dinoprostone