CD3 on CD28+ DN (CD4-CD8-) (P = 0.022, OR = 0.957, 95%CI = 0.922~0.993) and CD28 on activated Treg (P = 0.022, OR = 0.964, 95%CI = 0.935~0.995) had a negative causal relationship with breast cancer. This evidence concerns the gene CD4 and breast cancer.