The effect of vitamin D supplementation on the risk of breast cancer: a trial sequential meta-analysis

Observational studies suggest an inverse association between circulating vitamin D levels and risk of breast cancer. However, the potential benefits of vitamin D supplementation to reduce the risk of breast cancer remain controversial, based on the results of current randomized controlled trials (RCTs). The aim of this study was to evaluate the value of vitamin D supplementation on breast cancer prevention.

PubMed, Embase, and Cochrane library were searched from inception to February 2020. We performed a trial sequential meta-analysis of RCTs reporting the effect of vitamin D supplementation, with or without calcium, on the risk of breast cancer. The effect was estimated using a relative risk reduction threshold of 30%.

Eight trials comprising 72,275 participants were included in this study, with a median follow-up period ranging from 1 to 11.9 years. The median dosage of vitamin D supplementation was 967 IU per day (range 400-3704 IU per day) across the trials. This study yielded a relative risk of 1.04 (95% CI 0.85-1.29, P = 0.68) for the effect of vitamin D supplementation (6 trials, 33,472 participants), and 0.99 (95% CI 0.91-1.07, P = 0.73) for co-administration of vitamin D and calcium (4 trials, 41,957 participants). The effect estimate for vitamin D with or without calcium on breast cancer risk lay within the futility boundary, indicating that vitamin D supplementation does not alter the relative risk by 30% or more.

Our analyses suggest that vitamin D supplementation, with or without calcium, does not reduce breast cancer risk by 30% or more. Future trials with similar designs are unlikely to alter this finding.