Abstract 5635: Vitamin D supplementation decreases serum 27-hydroxycholesterol and expression of CYP27A1 in tumors of breast cancer patients

Abstract

Abstract The goal of this study was to investigate whether vitamin D regulates the conversion of cholesterol to 27-hydroxycholesterol (27HC), an endogenous selective estrogen receptor modulator (SERM) that can act as a driver of estrogen receptor positive (ER+) breast cancer, particularly in post-menopausal women with low circulating estrogen levels. The hypothesis of this study was that the active metabolite of vitamin D, calcitriol, can inhibit expression of CYP27A1, the synthesizing enzyme for 27HC, thereby decreasing the concentration of 27HC in the blood. Both 27HC and 25-hydroxyvitamin D (25OHD) were quantified by LC-MS/MS in the serum of 29 breast cancer patients, 26 of which had ER+ cancer, pre- and post-treatment with either a low dose (control) of 400 IU vitamin D or a high dose of 10,000 IU vitamin D per day during the neoadjuvant period, which ranged between 7 and 37 days. In addition to these blood samples, tissue biopsies pre-treatment and the excised tumor collected post-treatment were tested for gene expression by microarray analysis. A significant increase (p = 4.3E-5) was observed in serum 25OHD for patients who received the high dose vitamin D compared to those who received the low dose, whose 25OHD values remained stable. A greater decrease (p = 1.7E-1) was observed in serum 27HC for the high dose group compared to the low dose group, with greater decreases in 27HC on average for those with larger increases in 25OHD concentration. Gene expression measurements showed a decrease in CYP27A1 expression (p = 4.5E-1) in breast cancer tissue for the high dose group compared to the low dose group, with greater decreases in expression observed for patients on high dose vitamin D treatment for longer times. These preliminary data show good evidence that high dose vitamin D supplementation can decrease 27HC levels in the body by inhibiting expression of CYP27A1 and that the longer this treatment, the greater the effect. While larger scale studies are needed, the data in this study point to vitamin D supplementation as a possible simple method for inhibiting ER+ breast cancer growth and suggests this reduction in CYP27A1 expression as an additional pathway by which vitamin D can mitigate risk and improve outcomes for ER+ breast cancer patients. Citation Format: Catherine Going, Ludmila Alexandrova, Ken Lau, Christine Yeh, Melinda Telli, Kristin Jensen, David Feldman, Sharon Pitteri. Vitamin D supplementation decreases serum 27-hydroxycholesterol and expression of CYP27A1 in tumors of breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5635. doi:10.1158/1538-7445.AM2017-5635