摘要Objective:Despite cardiotoxicity overlap,the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits.Pegylated liposomal doxorubicin(PLD),a less cardiotoxic anthracycline,was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods:In this multicenter,phase Ⅱ study,patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m2)and cyclophosphamide(600 mg/m2),followed by four cycles of taxanes(docetaxel,90-100 mg/m2 or nab-paclitaxel,260 mg/m2),concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg)and pertuzumab(840 mg loading dose,then 420 mg)every 3 weeks.The primary endpoint was total pathological complete response(tpCR,ypT0/is ypN0).Secondary endpoints included breast pCR(bpCR),objective response rate(ORR),disease control rate,rate of breast-conserving surgery(BCS),and safety(with a focus on cardiotoxicity).Results:Between May 27,2020 and May 11,2022,78 patients were treated with surgery,42(53.8％)of whom had BCS.After neoadjuvant therapy,47[60.3％,95％confidence interval(95％CI),48.5％-71.2％]patients achieved tpCR,and 49(62.8％)achieved bpCR.ORRs were 76.9％(95％CI,66.0％-85.7％)and 93.6％(95％CI,85.7％-97.9％)after 4-cycle and 8-cycle neoadjuvant therapy,respectively.Nine(11.5％)patients experienced asymptomatic left ventricular ejection fraction(LVEF)reductions of ≥10％from baseline,all with a minimum value of＞55％.No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-proBNP),troponin I,or high-sensitivity troponin.Concluslons:This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC.Importantly,this regimen showed an acceptable safety profile,especially a low risk of cardiac events,suggesting it as an attractive treatment approach with a favorable risk-benefit balance.