Serum Vitamin D and Risk of Breast Cancer within Five Years

Abstract

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 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].

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.

Figure 1.

Distribution of 25(OH)D in cases and random subcohort (A). Hazard ratios and 95% confidence intervals for the association between 25(OH)D and breast cancer incidence within 5 y in the Sister Study (B). The hazard ratios are adjusted for batch, seasonal trends, race, education level, current hormonal birth control use, current hormone therapy use and type, menopausal status, physical activity, body mass index (BMI), osteoporosis, and a BMI × menopausal status interaction term. There are 1,600 cases and 1,822 participants in the random subcohort (including 67 cases) with complete covariate information (total $n=\mathrm{3,355}$).