For biomarker analysis, patients with mutations of PIK3CA (23%) or ERBB2 (7.0%) had shorter PFS. Response to previous anti-HER2 therapy (>6 months) (HR = 0.53, 95% CI 0.34–0.82), PIK3CA mutations (HR = 2.32, 95% CI 1.38–3.92), and ERBB2 mutations (HR = 5.18, 95% CI, 2.11–12.72) were significant predictors of PFS by multivariable analysis....In summary, our study showed the clinical efficacy and safety of a trastuzumab biosimilar plus chemotherapy, even in heavily pretreated HER2-positive MBC patients. The response duration of previous anti-HER2 treatment was an important clinical factor for the prediction of clinical efficacy in this population. PIK3CA and ERBB2 mutations were associated with shorter PFS...