Serum levels of vitamin D metabolites and breast cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

B103

Experimental and epidemiologic studies suggest that vitamin D metabolites (1,25-dihydroxyvitamin D [1,25(OH)₂D] and its precursor 25-hydroxyvitamin D [25(OH)D]) may reduce breast cancer risk. We examined subsequent breast cancer risk related to serum levels of these metabolites.In a cohort of women aged 55-74 years, who donated blood at baseline (1993-2001) in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, we identified 1005 incident breast cancer cases during follow-up through 2005 (mean time between blood draw and diagnosis = 3.9 years). Non-cases (n=1005) were frequency matched to the cases based on age and year of entry. Sample weights that accounted for unequal probabilities of selecting cases and non-cases were applied to make inferences that reflected the entire PLCO cohort. Using Cox proportional hazards modeling, we computed breast cancer relative risks (RR) and 95% confidence intervals (CI) by quintile for each metabolite. The RR of breast cancer for the highest quintile of 25(OH)D concentration vs. the lowest was 1.04 (95% CI=0.75-1.45), p(trend)=0.81. Similarly, the breast cancer RR for the highest quintile of 1,25(OH)₂D compared to the lowest was 1.23 (95% CI=0.91-1.68), p(trend)=0.14. Excluding the first two years of follow-up did not materially alter these estimates. There was also no evidence of inverse risk in older (≥60 years) vs. younger women (<60 years).In this prospective study of post-menopausal women, we did not observe an inverse association between circulating 25(OH)D or 1,25(OH)₂D and breast cancer risk, although we cannot exclude an association in younger women or with long-term or earlier exposure.