Serum Vitamin D and Risk of Breast Cancer within Five Years

Vitamin D is an environmental and dietary agent with known anticarcinogenic effects, but protection against breast cancer has not been established. 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. 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. We found that 25(OH)D levels were associated with a 21% lower breast cancer hazard (highest versus lowest quartile: adjusted ; 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 was associated with an 11% lower hazard [ (CI: 0.81, 0.99)]. These associations were particularly strong among postmenopausal women [ (CI: 0.57, 0.93) and (CI: 0.74, 0.93), respectively]. 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.