Researchers explored if circulating blood lymphocyte subsets have any effect on the survival of metastatic breast cancer (MBC) patients and assessed their predictive and prognostic ability by retrospectively analyzing the clinical data of 482 patients with MBC. Patients were grouped by molecular type of breast cancer. Outcomes revealed worse survival outcomes in significant correlation with higher circulating levels of CD4+ and CD3+ at first diagnosis in human epidermal growth factor receptor 2 (HER2)-overexpressing MBC. Increased anti-HER2 benefit in HER2-positive MBC was evident with low levels of plasma CD4+ and CD3+. Results thereby suggest these factors are effective predictive and prognostic markers of outcome in patients with MBC.