All biomarker subgroups associated with higher HER2 amplification or expression (HER2 IHC3+, HER2/CEP17 gene ratio ≥ 4, HER2 mRNA expression > median, and homogeneous HER2 IHC expression) showed numerically higher pCR rates compared with subgroups with lower HER2 levels, irrespective of treatment arm...Although our biomarker analysis did not identify a subgroup of patients that benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm. These analyses confirm the role of HER2 tumor biology and the immune microenvironment in influencing pCR in the neoadjuvant setting and reaffirm the molecular diversity of HER2-positive breast cancer.