Prediagnostic Serum Vitamin D and Breast Cancer

The active metabolite of vitamin D [i.e., 1,25(OH)2D] is a recognized modulator of cell proliferation and differentiation (1,2), and studies (3) have shown that it can reduce the incidence of mammary cancer in rats. Several mechanisms have been postulated for a protective effect of vitamin D on human breast cancer (3–8); however, epidemiologic studies (9–17) investigating dietary sources of vitamin D—and milk consumption in particular—have yielded inconsistent results in relation to breast cancer risk. Sunlight, the other source of vitamin D, has been postulated to exert a protective effect on the development of breast cancer on the basis of an ecologic correlation of age-adjusted breast cancer mortality rates and solar radiation exposure levels (5,18,19). The metabolites of vitamin D3 (cholecalciferol), originating from sunlight, and the metabolites of vitamin D2 (ergocalciferol), originating from dietary sources, are indistinguishable. Therefore, measurement of 1,25(OH)2D, the active metabolite and presumably the form through which any protective effect of vitamin D on breast cancer would operate, can be used to test this hypothesis. One previous human case-control study (20) of serum vitamin D measured after the diagnosis of breast cancer found lower levels among the case subjects.