Vitamin D, calcium, and breast cancer risk: a review.

Vitamin D and calcium are metabolically interrelated and highly correlated dietary factors. Experimental studies have shown their anticarcinogenic effects due to their participation in regulating cell proliferation, differentiation, and apoptosis in normal and malignant breast cells. Given the emerging interest in their potential roles in the etiology of breast cancer, we review the current epidemiologic literature on dietary and/or supplemental intakes of vitamin D, endogenous circulating levels of vitamin D, and dietary and/or supplemental intakes of calcium in relation to breast cancer risk. To place these studies in context, we also provide a brief review of other supporting epidemiologic evidence. Despite inconsistent results from the epidemiologic studies, several lines of evidence suggest that vitamin D and calcium may be involved in the development of breast cancer. Specifically, (a) there is some epidemiologic evidence for inverse associations between vitamin D and calcium intakes and breast cancer; (b) serum, plasma, and/or blood levels of vitamin D metabolites have been inversely associated with breast cancer risk in some studies; (c) high sunlight exposure, presumably reflecting vitamin D synthesis in the skin, has been associated with a reduced risk of breast cancer; (d) vitamin D and calcium intakes have been inversely related to breast density, an intermediate end point for breast cancer; (e) calcium has been associated with a reduced risk of benign proliferative epithelial disorders of the breast, putative precursors of breast cancer; and (f) certain polymorphisms of the vitamin D receptor might modify breast cancer susceptibility. To further confirm the potential protective effects of calcium and vitamin D on breast cancer, well-designed cohort studies and clinical trials are warranted.