Celecoxib concentration predicts decrease in prostaglandin E2 concentrations in nipple aspirate fluid from high risk women

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.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).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.Cyclooxygenases (COX)-1 and COX-2 may be present in breast tumors to catalyze the conversion of arachidonic acid to prostaglandins, prostacyclins, or thromboxanes. While COX-1 expression is constitutive, COX-2 is inducible [1] and is upregulated in a variety of tumors, including breast cancers [2]. Prostaglandin (PG)E2, which has tumor and cell growth promoting activity [3], is produced from arachidonic acid by either COX-1 or -2. Malignant breast tumors produce more PGE2 than benign breast tumors or normal breast tissue [2]. Women with breast cancer with TUMOR PGE2 levels above 15 ng/g appear to have a significantly worse survival rate than those with levels ≤ 15 ng/g [4].Nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, indomethacin and ibuprofen, inhibit both COX-1 and COX-2. Inhibition of COX-1 leads to a number of adverse effects, including gastrointestinal ulcers and renal toxicity [5]. Recent efforts have therefore focused on pharmacologic agents such as celecoxib, a clinically available medi