摘要Objective:To explore the prognosis-predictive influence of human epidermal growth factor receptor 2(HER2)-low status in breast cancer patients after neoadjuvant therapy(NAT).Methods:Consecutive patients with invasive breast cancer who underwent NAT and surgery from January 2009 to December 2020 at multiple centers were included.A modified CPS+EG scoring system that integrates HER2-low status,CPS+EGHlow was developed.Multiple scoring systems were compared via receiver operating characteristic curves with the area under curve(AUC),the Akaike information criterion,the C-index,and calibration curves.Results:A total of 2,141 patients were included:1,074,640,and 427 patients in the training,internal validation,and external validation groups,respectively.HER2-low patients had a significantly better breast cancer-specific survival(BCSS,P=0.008)and recurrence-free interval(RFI,P=0.030)compared to HER2-zero patients(P=0.038)but inferior outcomes than HER2-amplified ones(BCSS,P=0.002;RFI,P＜0.001).The CPS+EGHlow(AUC:0.846,0.817,0.901)could stratify patients according to BCSS in training,internal validation,and external validation group,respectively,overperforming pathological stage(PS)(AUC:0.746,0.779,0.754),CPS+EG(AUC:0.771,0.752,0.748),and Neo-Bioscore(AUC:0.783,0.777,0.786,all P＜0.05).Conclusions:HER2-low status showed a significant prognostic value in breast cancer patients after NAT.The CPS+EGHlow model significantly outperformed PS,CPS+EG,and Neo-Bioscore in clinical outcome prediction,which may guide further therapy targeting HER2-low.