Liu S, et al. - In this study, researchers aim to determine the role of tumor-infiltrating lymphocytes (TILs), particularly cytotoxic CD8+ T cells, in the prediction of outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer randomized to an antibody-based (trastuzumab) vs a small molecule–based (lapatinib) anti-HER2 therapy. This secondary analysis of phase 3 randomized clinical trial demonstrates that a low level of preexisting stromal cytotoxic T-cell infiltration in primary tumor biopsy specimens predicts women who benefit from an antibody- vs a small molecule–based drug intervention for HER2-positive breast cancer, in the metastatic setting.