Effect of COX-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer

摘要

Aromatase (CYP19) is responsible for estrogen biosynthesis, and CYP- 19 and cyclooxygenase-2 (COX-2) are both overexpressed in human breast cancers. Prostaglandin activates the CYP19 promotor and increases gene expression therefore we hypothesized that celecoxib, a selective COX-2 inhibitor, will decrease PG and decrease the expression of CYP19. To test this hypothesis, celecoxib was administered to breast cancer patients after the initial core biopsy tumor tissue and then tumor tissue was collected at the definitive surgery on OSU protocol 0125. A total of 8 breast cancer patients were enrolled until December 20, 2004 when the cardiovascular risks associated with celecoxib were made public. Accrual was suspended and the restarted in July 2005 with a revised protocol and consent form describing the cardiovascular risks. The trial was closed November 13, 2006 due to lack of accrual. There were no adverse events recorded during celecoxib administration. With only 8/34 (23%) of patients enrolled, there have no analysis of gene expression of CYP19. This trial failed to accrue, in part, over concerns about the cardiovascular risks.