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Introduction  Experimental evidence suggests a protective role for circulating 25-hydroxyvitamin D (25(OH)D) in breast cancer development, but the results of epidemiological studies have been inconsistent.    Methods  We conducted a case-control study nested within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Mammary Screening Cohort. Blood samples were collected at enrollment, and women were followed up for breast cancer ascertainment. In total, 1,585 incident breast cancer cases were individually-matched to 2,940 controls. Of these subjects, 678 cases and 1,208 controls contributed two repeat blood samples, at least one year apart. Circulating levels of 25(OH)D were measured, and multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.    Results  No association was observed between circulating levels of 25(OH)D and overall breast cancer risk (multivariate-adjusted model OR = 0.94, 95% CI = 0.76-1.16 for the highest vs. lowest quintile,  p  trend  = 0.30). The temporal reliability of 25(OH)D measured in repeat blood samples was high (intraclass correlation coefficients for season-adjusted 25(OH)D > 0.70). An inverse association between 25(OH)D levels and breast cancer risk was observed among women who were ≤ 45 years of age (OR Q5-Q1  = 0.48, 95% CI = 0.30-0.79,  p  trend  = 0.01) or premenopausal at enrollment (OR Q5-Q1  = 0.67, 95% CI = 0.48-0.92,  p  trend  = 0.03).    Conclusions  Circulating 25(OH)D levels were not associated with breast cancer risk overall, although we could not exclude the possibility of a protective effect in younger women. Recommendations regarding vitamin D supplementation should be based on considerations other than breast cancer prevention.

Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case-control study