The Effects of Vitamin D on the Breast Cancer Tumor Microenvironment

The intricate and diverse TME within breast cancer (BC) comprises a complex amalgamation of cell populations, encompassing immune cells, cancer-associated fibroblasts, cancer stem cells and the extracellular matrix. These constituents have profound influence over tumor progression and metastasis. Vitamin D (VD) is increasingly recognized as a multifunctional hormone, with strong clinical and epidemiological evidence supporting its protective role against cancer, particularly BC. Although its anti-neoplastic effects in BC have been widely studied, few investigations have thoroughly explored its influence within the tumor microenvironment (TME). This review seeks to address that gap by clarifying the current understanding of VD's regulatory functions in the TME of BC. The pivotal anti-cancer functions of VD comprise a spectrum of activities, influencing cell cycle regulation, chemoprotection, differentiation, apoptosis, proliferation, angiogenesis, as well as having anti-metastatic and anti-invasive properties. In this review, we comprehensively outline VD's anti-cancer mechanisms within the context of the BC TME, meticulously detailing its regulatory impact on cancer-associated fibroblasts, adipocytes, immune cells, cancer stem cells, and the extracellular matrix. This unique perspective highlights the potential of using VD to re-program the TME and enhance the efficacy of current BC therapeutics.