• The Role Of Vitamin D Receptor (VDR) As A Therapeutic Target In Breast Cancer: A Review Study
  • Mohammad Mahdi Elahiyan,1,* Mahsa Rafieipour,2
    1. Student Research Committee, School of Allied Medical Sciences, Iran University of medical sciences, Tehran, Iran
    2. Msc Student, College Of Science, Faculty Of Biotechnology, University Of Tehran, Tehran, Iran


  • Introduction: Breast cancer is the most common cancer among women worldwide, accounting for 11.6% of all cancers diagnosed in 2020. Vitamin D, due to its vital role in calcium homeostasis, plays a significant role in cellular processes, particularly in breast tissue. These processes are mediated through the Vitamin D Receptor (VDR), a nuclear receptor. The aim of this review study is to investigate the role of VDR as a potential therapeutic target in breast cancer.
  • Methods: A search of Google Scholar and PubMed using the keywords "vitamin D," "breast cancer," and "therapeutics" was conducted to identify relevant literature. Inclusion criteria were: keywords in the abstract or title, English language, full-text availability, and relevance to the research topic. Twenty articles were selected for final analysis.
  • Results: Given its expression in breast cancer cells, VDR is a potential therapeutic target. Its action involves inhibiting cancer cell growth via mechanisms like G0/G1 cell cycle arrest and increased production of CDK inhibitors p21 and p27. Furthermore, VDR promotes programmed cell death (apoptosis) by reducing BCL-2 levels, releasing cytochrome c, and activating caspases. Its influence on signaling pathways related to cell invasion, angiogenesis, and the tumor microenvironment suggests a role in suppressing metastasis. VDR expression levels are clinically relevant, impacting both prognosis and treatment outcomes; lower expression is linked to more aggressive tumors. ER+ breast cancers, in particular, appear more sensitive to therapies incorporating vitamin D. Despite these encouraging observations, some research has produced contradictory results, indicating that VDR and vitamin D may not positively affect survival rates in breast cancer.
  • Conclusion: Evidence suggests that VDR expression in breast cancer cells indicates its potential therapeutic relevance. VDR exerts antiproliferative effects on cancer cells, partly through G0/G1 cell cycle arrest and upregulation of CDK inhibitors p21 and p27. Moreover, it enhances apoptosis in these cells through mechanisms involving BCL-2 downregulation, cytochrome c release, and caspase activation. VDR influences cell invasion, angiogenesis, and the tumor microenvironment via modulating specific signaling pathways, thereby suppressing metastasis in breast carcinogenesis. VDR expression is linked to patient prognosis and treatment response in breast cancer; decreased VDR expression correlates with more aggressive tumor behavior. Furthermore, ER+ cancers are more responsive to vitamin D-based treatments. However, the evidence supporting a definitive effect of VDR and vitamin D on breast cancer outcomes, including mortality and/or survival, remains inconsistent, with some studies failing to demonstrate a positive impact on mortality.
  • Keywords: Breast Neoplasms, Vitamin D, Therapeutics