Treatment of breast cancer (BC) is becoming stratified on the basis of classified treatment. Different from trastuzumab emtansine (T-DM1) as 2nd-line anti-human epidermal growth factor receptor 2 (HER2) treatment is recommended by foreign guidelines and clinical practice, more patients in China are receiving anti-HER2 tyrosine kinase inhibitor (TKI) as 2nd-line anti-HER2 targeted therapy for metastatic BC, which raises the issue of subsequent targeted therapy after TKI failure, the preferred regimen and how to optimize it. Evidence from high-quality randomized controlled clinical trials is lacking up to now, but in clinical practice this stratified subgroup patients need to be treated. Failure to TKI treatment is first described in the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) Guidelines 2022, based on existing clinical trials data, real-world research data and expert opinions on HER2-positive metastatic BC, although there are no Level I recommendations and Level II options include anti-HER2 antibody-drug conjugate (ADC) (2A evidence), pertuzumab and trastuzumab plus other (non-taxane) chemotherapy (2A evidence), switching to another TKI plus chemotherapy (2A evidence) and entering strictly designed clinical trials. In the era of "after anti-HER2 TKI", there will be more results of randomized controlled clinical trials and real-world researches as evidences to guide the therapy in the future, and clinicians must ensure accurate classification and precise stratification of patients to deliver optimized, precise subsequent therapy.
