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Objective: Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human epidermal growth factor receptor 2 (HER2) therapy (lapatinib or trastuzumab) plus chemotherapy or chemotherapy alone in patients who were previously treated with trastuzumab-containing regimens and investigate factors associated with effectiveness.And we further show the effectiveness of the two anti-HER2 therapy groups.Methods: A total of 342 HER2-positive metastatic breast cancer (MBC) patients whose disease progressed during prior anti-HER2 (trastuzumab) and standard chemotherapy therapy from Department of Breast Oncology,the Fifth Medical Center of Chinese PLA General Hospital,from August 2010 to December 2016 were included.Seventy-eight patients received standard chemotherapy only,148 patients continued to receive trastuzumab and switched to other chemotherapy drugs,and 116 patients received tyrosine-kinase inhibitors (TKIs;lapatinib) and chemotherapy.The main outcome measures were progression-free survival (PFS),overall response rate (ORR),and clinical benefit rate (CBR),Subgroup analyses were conducted to identify patient characteristics associated with the greatest clinical benefit.Results: After a median follow-up of 26.2 (range,2.0-56.0) months,PFS significandy improved with anti-HER2 therapy compared with chemotherapy alone: median 6.0 months with lapatinib[95％ confidence interval (95％ CI),4.53-7.47],4.5 months with trastuzumab (95％ CI,3.99-5.01) vs.3.0 months with chemotherapy alone (95％ CI,2.42-3.58);stratified hazard ratio (HR)=0.70,95％ CI,0.60-0.81;P＜0.0001.The ORR values were 33.6％,25.0％ and 12.8 ％,respectively,the CBR values were 60.3％,48.6％ and 26.9％,respectively.The effectiveness of lapatinib group and trastuzumab group were further analyzed.In multivariate analysis,lapatinib group was associated with a longer PFS,after controlling other potential confounders (HR=0.68,95％ CI,0.52-0.90;P=0.006).Conclusions: The combination of TKIs and chemotherapy was effective in this cohort previously treated with trastuzumab treatment.Therefore,TKIs combined with chemotherapy is an option for Chinese HER2-positive MBC patients previously treated with trastuzumab treatment.