Human breast carcinomas represent a heterogeneous group of tumours, distinct in behaviour, outcome and response to therapy. Basal-like breast carcinomas correspond to an intriguing subgroup recognized by the expression of molecules usually found in basal/myoepithelial cells of normal breast and are highly associated with a poor prognosis, which remain until now with no specific therapy.

Vitamin D is the strongest natural anti-proliferative compound. A large number of studies in a wide spectrum of cancers, including epidemiological, in vitro and animal models, demonstrate that the active form of vitamin D has anti-cancer benefits, both during progression as well as against metastases. The identification of the vitamin D receptor (VDR) in breast cancer cells suggested that this receptor might represent a target for breast cancer therapy, thus raising considerable interest in the therapeutic use of VDR agonists for treatment of breast cancer with several molecules currently under clinical trials. Clinically relevant biomarkers that are modulated by vitamin D in human breast cancer cells include BRCA1, p21, p53, c-Myc, and cyclin D1. Of particular interest, the effects of vitamin D are not dependent on functional p53 and are not restricted to estrogen-dependent cells, both characteristics of basal-like breast carcinomas. Recent studies show that Vitamin D is able to down-regulate typical myoepithelial/basal markers in breast cancer cells and that mouse lacking VDR display high levels of basal-like proteins in the mammary gland. These findings demonstrate that Vitamin D affects breast cancer cells phenotype and suggest that it may reverse myoepithelial/basal features associated with the aggressiveness of basal-like breast cancer.

The main goal of this project is to unravel the link between Vitamin D and basal-like carcinomas, gaining insight into its capacity to modulate their aggressive biological behaviour. In conformity with the project results, vitamin D or analogues may constitute a new therapy for prevention and/or treatment of this specific group of tumours.