Several studies show that
triple-negative breast cancer (TNBC) patients have the lowest
vitamin D concentration among all
breast cancer types, suggesting that this
vitamin may induce a protective effect against TNBC. This effect of the active metabolite of
vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(
OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis,
inflammation, angiogenesis, invasion and
metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated
breast cancer type 1 susceptibility (BRCA1) gene, 1,25(
OH)2D may induce protective effects by activating its receptor and inactivating
cathepsin L-mediated degradation of
tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in
DNA double-strand break repair and contributing to
genome stability. Similar effects can be induced by the interaction of 1,25(
OH)2D with
proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of
vitamin D in TNBC to assess its preventive and therapeutic potential.