HER2-low as a unique subgroup in breast cancer: insights from neoadjuvant chemotherapy response and survival analysis.

Abstract

Aims: Traditional breast cancer treatment relies on binary human epidermal growth factor receptor 2 (HER2) classification, while HER2-low breast cancer represents an intermediate subgroup. Given the efficacy of novel antibody-drug conjugates, this study aimed to clarify whether HER2-low breast cancer is biologically and clinically distinct from HER2-0 disease, especially in response to neoadjuvant chemotherapy.

Methods: A retrospective analysis was performed on 1274 early breast cancer patients receiving neoadjuvant chemotherapy. Patients were divided into HER2-0 (n=210), HER2-low (n=590) and HER2-positive (n=474) groups. Clinicopathological features, pathological complete response (pCR) and long-term survival were compared.

Results: HER2-low tumours were predominant in Luminal A-like subtype, with lower pCR rate (14.7%) than HER2-0 (27.6%) and HER2-positive (35.5%) groups. Hormone receptor (HR)-positive status was associated with higher pCR in HER2-low patients. HER2-low tumours showed higher lymph node metastasis and lower Ki-67 levels. No significant differences in disease-free survival (DFS) or overall survival (OS) were observed between HER2-low and HER2-0 groups, with distinct prognostic factors for each subgroup.

Conclusions: HER2-low breast cancer exhibits unique clinicopathological features and differential chemotherapy response. However, it shows similar survival to HER2-0 disease with standard neoadjuvant chemotherapy. The clinical value of HER2-low status may rely on targeted antibody-drug conjugate therapy.