Tumor Expression of Vitamin D Receptor and Breast Cancer Histopathological Characteristics and Prognosis

Purpose: Our previous work has shown low serum 25-hydroxyvitamin D concentrations in association with aggressive breast cancer subtypes. Vitamin D receptor (VDR) is central for vitamin D-mediated transcription regulation. Few studies have examined breast VDR expression with tumor characteristics or patient survival. Experimental Design: VDR expression in breast tumor tissue microarrays was determined by immunohistochemistry in 1,114 female patients as low, moderate, and strong expression based on an immunoreactive score, and examined with histopathologic tumor characteristics and survival outcomes including progression-free survival, breast cancer-specific survival, and overall survival. Results: A majority (58%) of breast tumors showed moderate or strong VDR expression. VDR expression was inversely related to aggressive tumor characteristics, including large tumor size, hormonal receptor (HR) negativity, and triple-negative subtype (P < 0.05). In addition, VDR expression was also inversely related to Ki-67 expression among patients older than 50 years. Nevertheless, VDR expression was not associated with any patient survival outcomes examined. Conclusions: In a large patient population, VDR expression is inversely associated with more aggressive breast cancer, but not with breast cancer survival outcomes. The present findings of VDR expression are consistent with our previous results of circulating vitamin D biomarkers, which provide two converging lines of evidence supporting the putative benefits of vitamin D against aggressive breast cancer. Because of the observational nature of our analyses, future studies are warranted to establish the causality of the reported associations. (C) 2016 AACR.