AbstractBackgroundThe changes in prognostic factors and clinicopathological characteristics of residual disease following neoadjuvant therapy (NAT) for breast cancer are important references for postoperative adjuvant therapy. The analyses of the relationship between the clinicopathological characteristics of residual diseases and the prognosis were not comprehensive in most previous studies. This study aimed to determine how prognostic factors changed following NAT and the impact of clinicopathological characteristics of residual disease on the prognosis of human epidermal growth factor receptor 2 (HER2)‐positive breast cancer.MethodsThe study comprised 350 consecutive patients with HER2‐positive breast cancer who had residual disease after surgery following NAT. The independent risk factors affecting the prognosis of HER2‐positive breast cancer were analyzed using univariate and multivariate Cox regression analyses. Chi‐square test and binary logistic regression were used to analyze the influencing factors of HER2 loss following NAT.ResultsThe expression of prognostic factors changed significantly following NAT. A total of 44 patients (12.6%) had HER2 loss. HER2 status (immunohistochemistry (IHC) 3+ vs. IHC 2+/FISH+,p< 0.001) at baseline was associated with HER2 loss. In this investigation, the HER2 loss did not affect the prognosis. In univariate analysis, the decrease in Ki‐67 (p< 0.001) after NAT was associated with improved prognosis, but this influence was lost in the Cox proportional hazards model. The ypN stage (p< 0.001), postoperative ER status (p= 0.020), Miller–Payne grade (p= 0.007), and targeted therapy (p= 0.003) were all independent prognostic factors.ConclusionsER, PR, HER2, and Ki‐67 changed significantly after NAT, but no impact of these changes on DFS was observed in this study. Postoperative N stage, postoperative ER status, MP grade, and targeted therapy were independent prognostic factors in patients with HER2‐positive breast cancer after NAT.