Effect of Vitamin D Supplementation on Risk of Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective: Laboratory findings indicated that vitamin D might have a potent protective effect on breast cancer, but epidemiology studies reported conflicting results. The aim of the study was to conduct a systematic review and meta-analysis to clarify the efficacy of vitamin D supplementation on risk of breast cancer. Methods: MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, , and abstracts of three major conferences were searched (up to December 8, 2020). Parallel randomized controlled trials (RCTs) examining the efficacy of vitamin D supplementation on risk of breast cancer or change of mammography compared with placebo in females were included. Data were meta-analyzed using a random-effects model. Bayesian meta-analysis was conducted to synthesize the results using data from observational studies as priors. Results: Seven RCTs were identified for effect of vitamin D on risk of breast cancer, with 19,137 females included for meta-analysis. No statistically significant effect of vitamin D on risk of breast cancer was found in classical random-effects meta-analysis (risk ratio = 1.04, 95% confidence interval: 0.84-1.28, p = 0.71). When Bayesian meta-analyses were conducted, results remained non-significant. There was no statistically significant effect of vitamin D on mammography density observed: mean difference = 0.46, 95% confidence interval: -2.06 to 2.98, p = 0.72. Conclusion: There is insufficient evidence to support the efficacy of vitamin D supplementation in breast cancer risk and change of mammography density. The protective effect of vitamin D on risk of breast cancer from previous observational studies may be overestimated. Systematic Review Registration: PROSPERO, identifier CRD42019138718.