In our meta-analysis, HER2-targeted therapy was associated with prolonged OS (HR 0.47; 95% CI, 0.39–0.56) in patients with HER2-positive breast cancer and IMD, with an iORR of 22% (95% CI, 14–30%), an iDCR of 62% (95% CI, 55–69%), an iCRR of 0% (95% CI, 0–0.01%), and a grade 3+ adverse event rate of 26% (95% CI, 11–45%). This evidence concerns the gene ERBB2 and breast cancer.