Vitamin D and breast cancer: Past and present

Area of Science:

• Oncology
• Endocrinology
• Molecular Biology

Background:

• The vitamin D receptor (VDR) and its active ligand, 1,25-dihydroxyvitamin D (1,25D), are present in mammary glands and breast cancer.
• Pre-clinical studies show 1,25D influences mammary gland development and cancer susceptibility, affecting cell cycle, apoptosis, autophagy, and differentiation.
• Vitamin D deficiency is prevalent in breast cancer patients, potentially increasing disease risk and progression.

Purpose of the Study:

• To validate 1,25D-responsive targets in vivo, particularly those regulating key cellular processes.
• To investigate the role of VDR expression and 1,25D action in breast cancer transformation.
• To clarify conflicting clinical data on vitamin D responsiveness in established tumors by analyzing VDR actions in specific breast cancer subtypes.

Main Methods:

• Characterization of 1,25D responsive targets in normal mammary cells and breast cancers.
• Utilizing in vitro and in vivo model systems of carcinogenesis.
• Employing genomic, proteomic, and metabolomic analyses to understand vitamin D-regulated pathways.

Main Results:

• Validation of 1,25D-regulated targets in vivo remains challenging.
• Evidence suggests VDR expression and 1,25D actions are altered during breast cancer transformation.
• Clinical data on vitamin D's effect on established tumors is limited and inconclusive.

Conclusions:

• Understanding vitamin D's role in breast cancer requires analyzing VDR actions within specific molecular subtypes due to tumor heterogeneity.
• Comprehensive analyses of vitamin D-regulated pathways using multi-omics approaches in model systems are essential.
• Further research is needed to elucidate the complex interplay between vitamin D, VDR, and breast cancer progression.