Many epidemiological studies have indicated a protective role of high serum vitamin D levels against the development of breast cancer.  However, these findings are not always consistent and the molecular basis for such a link remains unclear.  We have used a breast explant system whereby breast tumour tissue and adjacent non-malignant breast tissue samples were treated ex vivo with either 1,25D (active metabolite) or 25D (inactive pre-metabolite present in human serum).  The molecular and biological effects of these treatments were compared using IHC or RNA expression analyses.  Responses between paired tumour/normal breast samples were examined, as well as inter-individual differences in tissue responses.

Results indicate that almost all breast tumour and non-malignant samples responded well to 1,25D in terms of target gene induction and reductions in tissue proliferation, although the responses to 25D were much more varied between tissues.  This may indicate an inability of some breast tissues to locally convert 25D to 1,25D.  Ongoing work involves the identification and characterisation of several novel vitamin D gene targets in the breast identified through microarray analyses.  This work may provide an understanding to the disparity between some vitamin D and breast cancer association studies.