In the phase III MARIANNE study, biomarkers related to the HER2 pathway (HER2 and HER3 mRNA expression levels, PIK3CA mutation status, PTEN H-score and protein expression level, and tumor heterogeneity) were not predictive of PFS benefit in MBC patients administered first-line treatment with T-DM1 with or without pertuzumab versus trastuzumab plus a taxane. This evidence concerns the gene PTEN and neoplasm.