Vitamin D actions in mammary gland and breast cancer

Vitamin D deficiency is common in breast cancer patients, and some evidence suggests that low vitamin D status enhances the risk for disease development or progression. In addition to receptors for classic steroid hormones such as estrogen and progesterone, the vitamin D receptor (VDR) and its ligand 1,25(OH)2D modulate normal mammary gland development and sensitivity to carcinogenesis. Genomic profiling has characterized many 1,25(OH)2D responsive targets in normal mammary cells and in breast cancers, providing insight into the molecular actions of 1,25(OH)2D and the VDR in the regulation of cell cycle, apoptosis, and differentiation. Newer areas of emphasis regarding the effects of vitamin D on breast cancer include its effects on estrogen signaling, cellular metabolism, and cancer stem cells. Model systems of carcinogenesis have provided evidence that both VDR expression and 1,25(OH)2D actions change with transformation but clinical data regarding vitamin D responsiveness of established tumors is limited. Because breast cancer is heterogeneous, analysis of VDR actions in specific molecular subtypes of the disease is helping to clarify the conflicting data. Genomic, proteomic, and metabolomic analyses of in vitro and in vivo model systems are clearly warranted to comprehensively understand the network of vitamin D-regulated pathways in the context of breast cancer.