The Role of Vitamin D and its Receptor in Breast Cancer: A Comprehensive Review of the Connection and Potential Implications

Abstract

Vitamin D and its receptor have attracted significant attention due to their potential roles in various biological processes, including breast cancer. Numerous studies, conducted both in vivo and in vitro, have demonstrated that vitamin D and its analogues exert control over diverse cellular mechanisms in both healthy and breast cancer cells. As a steroid hormone, vitamin D requires binding to the vitamin D receptor (VDR), a specific nuclear receptor. The VDR, in conjunction with RXR, forms a heterodimeric complex that binds to the vitamin D response elements (VDREs) on DNA, thereby regulating the transcription of genes responsive to vitamin D. Remarkably, VDR governs the expression of more than 500 genes. Investigations have revealed that vitamin D and its analogues exert regulatory effects on various hormone receptors in breast cancer, influencing treatment response and augmenting cancer cell sensitivity to therapeutic medications. With VDR being expressed in almost all tissues, the significance of vitamin D in cancer biology has been widely acknowledged. Moreover, breast cancer cells themselves express VDR. The identification of the enzyme system responsible for producing 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in breast tissue has shed light on the impact of vitamin D on both normal breast tissue and breast cancer cells. Furthermore, evidence indicates that inadequate exposure to solar radiation increases the risk of developing cancer. Given the escalating incidence of breast cancer and the widespread prevalence of vitamin D deficiency, this review aims to comprehensively explore the intricate connection between vitamin D, its receptor, and the likelihood of breast cancer development.