Epidemiologic data have demonstrated that breast cancer incidence is inverselycorrelated with indices of vitamin D status,including ultraviolet exposure,whichenhances epidermal vitamin D synthesis.The vitamin D receptor (VDR) is ex-pressed in mammary epithelial cells,suggesting that vitamin D may directly influ-ence sensitivity of the gland to transformation.Consistent with this concept,invitro studies have demonstrated that the VDR ligand,1,25-dihydroxyvitamin D (1,25D),exerts negative growth regulatory effects on mammary epithelial cells thatcontribute to maintenance of the differentiated phenotype.Furthermore,deletionof the VDR gene in mice alters the balance between proliferation and apoptosis inthe mammary gland,which ultimately enhances its susceptibility to carcinogenesis.In addition,dietary supplementation with vitamin D,or chronic treatment withsynthetic VDR agonists,reduces the incidence of carcinogen-induced mammarytumors in rodents.Collectively,these observations have reinforced the need tofurther define the human requirement for vitamin D and the molecular actions ofthe VDR in relation to prevention of breast cancer. Epidemiologic data have demonstrated that breast cancer incidence is inverselycorcorlated with indices of vitamin D status, including ultraviolet exposure, whichenhances epidermal vitamin D synthesis. Vitamin D receptor (VDR) is ex-pressed in mammary epithelial cells, suggesting that vitamin D may directly influ -ence sensitivity of the gland to transformation. Consistent with this concept, invitro studies have demonstrated that the VDR ligand, 1,25-dihydroxyvitamin D (1,25D), exerts negative growth regulatory effects on mammary epithelial cells thatcontribute to maintenance of the differentiated phenotype.Furthermore, deletionof the VDR gene in mice alters the balance between proliferation and apoptosis inthe mammary gland, which ultimately enhances its susceptibility to carcinogenesis.In addition, dietary supplementation with vitamin D, or chronic treatment withsynthetic VDR agonists, reduces the incidence of carcinogen -induced mammary tumors in rodents. Collectively, these signals have reinf orced the need tofurther define the human requirement for vitamin D and the molecular actions of the VDR in relation to prevention of breast cancer.