Two-sample MR results showed that 25(OH)D levels were not associated with prognosis in overall breast cancer (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.73–1.19, IVW exam) and estrogen receptor positive (ER+) breast cancers (OR = 1.12, 95% CI = 0.77–1.63, IVW exam) and were protective associated with prognosis in estrogen receptor negative (ER−) breast cancers (OR = 0.55, 95% CI = 0.34–0.87, IVW exam). This evidence concerns the gene ESR1 and breast cancer.