Abstract B50: Differential influence of vitamin D on the tumor promoting eicosanoid PGE2 in women at increased breast cancer risk

Abstract

Abstract Numerous lines of evidence point to the tumor promoting properties of prostaglandin (PG)E2. Preclinical studies have demonstrated the ability of both vitamin D (vitD) and celecoxib to downregulate the eicosanoid. We previously reported that vitD, but not the combination, significantly downregulated PGE2 in normal risk women. We hypothesized that there would be a similar or greater benefit of vitD alone, or in combination with celecoxib, in women at increased breast cancer risk. 40 women at increased breast cancer risk were prospectively enrolled and randomized in double blind fashion for one month (postmenopausal) or one menstrual cycle (premenopausal) to one of four daily treatment regimens: placebo, 400 IU vitD, 2000 IU vitD, or 2000 IU vitD + 400 mg celecoxib. Breast nipple aspirate fluid (NAF) and serum were collected. Both breast specific and systemic levels of PGE2 were measured. There was a significant increase (p=.02) in circulating levels of vitD after treatment in women receiving 2000 IU vitD with or without celecoxib, but not in women receiving placebo or 400 IU vitD. Celecoxib levels increased in those treated with celecoxib but not in the other groups. In the breast, as reflected in NAF, there was a 20% increase (p=.07) in PGE2 after treatment with 2000 IU vitD, with little change after treatment in the other groups. No treatment significantly changed circulating levels of PGE2. These findings suggest that, unlike in normal risk women, 2000 IU vitD may increase levels of a key cancer promoting enzyme in women of increased breast cancer risk. Supported in part with funds from the Komen Foundation and the Department of Defense. Citation Format: Wenyi Qin, Charles Walker, Edward Sauter. Differential influence of vitamin D on the tumor promoting eicosanoid PGE2 in women at increased breast cancer risk. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B50.