Abstract
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+EGH(low) 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+EGH(low) (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+EGH(low) model significantly outperformed PS, CPS+EG, and Neo-Bioscore in clinical outcome prediction, which may guide further therapy targeting HER2-low.