Impact of HER2-Low Status on Pathologic Complete Response and Survival Outcome Among Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Purpose: This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment.

Methods: This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed.

Results: Patients with HER2-low tumors were more likely to be older ( = 0.081), have a lower histological grade ( < 0.001), and have hormone receptor (HorR)-positive tumors ( < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups. The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test -value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; < 0.001). Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 ( = 0.042) and 0.728 ( = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; = 0.953).

Conclusion: Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors. Further investigation into biological differences is warranted.