The relationship between vitamin D and breast cancer incidence and natural history.

Endocrine action of vitamin D and its role in calcium homeostasis and bone health are well known. The discovery that breast epithelial cells possess the same enzyme system as the kidney, permitting local manufacture of active vitamin D (1,25 dihydroxyvitamin D, or 1,25[(OH)(2)D]) from circulating precursors 25 hydroxyvitamin D [25(OH)D], has suggested an autocrine role for vitamin D, as well. Preclinical and ecologic studies support a role of vitamin D in prevention of breast cancer. Correlative study results of vitamin D intake or measurement of 25(OH)D, the long-lived precursor, are mixed but suggest a protective effect in premenopausal women. The large Women's Health Initiative failed to show any reduction in breast cancer incidence in postmenopausal women with a modest amount of vitamin D supplementation. Lack of effect, however, may have been related to trial design. A recent report also suggests that vitamin D may reduce breast cancer recurrence and mortality. Finally, vitamin D is being investigated as a means to reduce aromatase inhibitor-induced joint symptoms.