Celecoxib in Women at Increased Breast Cancer Risk
Annual rept. 1 Oct 2001-30 Sep 2002
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Cyclooxygenase COX-l and COX-2, are present in breast tumors and catalyze the conversion of arachadonic acid to prostaglandins. Prostaglandin E2 PGE2 has tumor and cell growth promoting activity, and is overexpressed in human breast cancer. We proposed a pilot study of celecoxib administered to women at increased breast cancer risk, defined as a projected 5 year Gail model risk of invasive breast cancer 1.66, as well as women with a history of ductal carcinoma in situ or invasive breast cancer. Our hypothesis is that celecoxib will be concentrated in breast fluid compared to corresponding plasma, and that it will decrease POE2 levels in nipple aspirate fluid NAF and in plasma. Our Specific Aims are to determine if 1 celecoxib is delivered to the breast, and 2 PGE2 levels in NAF and plasma increase after a 2 week course of celecoxib, then return to baseline 2 weeks after stopping the medication. Both pre- and postmenopausal women undergo nipple aspiration and blood draw three times before, 2 weeks after starting celecoxib, and 2 weeks after stopping the medication. Each woman serves as her own control. Thus far we have enrolled 11 women on trial. NAF has been collected successfully in all subjects at each time point. POE2 levels were measurable in all NAF samples, and were significantly higher in NAF than in matched plasma. During the coming year, we hope is to determine if PGE2 levels significantly decrease after celecoxib administration, and if they return to baseline 2 weeks after discontinuing medication.
- Medicine and Medical Research