Ultimately, the analysis results from IVW showed that the genetic prediction of IgD- CD27- AC (atypical memory B cells) (OR = 1.317; 95% CI = 1.057–1.640; P = .014) and CD27 on IgD + CD38- unsw mem (OR = 1.071; 95% CI = 1.008–1.139; P = .027) were associated with a decreased risk of HER2-positive breast cancer. This evidence concerns the gene CD27 and breast cancer.