Serum Vitamin D and Risk of Breast Cancer within Five Years

BACKGROUND: Vitamin D is an environmental and dietary agent with known anticarcinogenic effects, but protection against breast cancer has not been established. OBJECTIVE: We evaluated the association between baseline serum 25-hydroxyvitamin D [25(OH)D] levels, supplemental vitamin D use, and breast cancer incidence over the subsequent 5 y of follow-up. METHODS: From 2003–2009, the Sister Study enrolled 50,884 U.S. women 35–74 y old who had a sister with breast cancer but had never had breast cancer themselves. Using liquid chromatography–mass spectrometry, we measured 25(OH)D in serum samples from 1,611 women who later developed breast cancer and from 1,843 randomly selected cohort participants. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of developing breast cancer using Cox proportional hazards models. RESULTS: We found that 25(OH)D levels [Formula: see text] were associated with a 21% lower breast cancer hazard (highest versus lowest quartile: adjusted [Formula: see text]; CI: 0.63, 0.98). Analysis of the first 5 y of follow-up for all 50,884 Sister Study participants showed that self-reported vitamin D supplementation [Formula: see text] was associated with an 11% lower hazard [[Formula: see text] (CI: 0.81, 0.99)]. These associations were particularly strong among postmenopausal women [[Formula: see text] (CI: 0.57, 0.93) and [Formula: see text] (CI: 0.74, 0.93), respectively]. CONCLUSIONS: In this cohort of women with elevated risk, high serum 25(OH)D levels and regular vitamin D supplement use were associated with lower rates of incident, postmenopausal breast cancer over 5 y of follow-up. These results may help to establish clinical benchmarks for 25(OH)D levels; in addition, they support the hypothesis that vitamin D supplementation is useful in breast cancer prevention. https://doi.org/10.1289/EHP943