Clinicopathological features and prognosis of HER2 low-expression breast cancer: a single-center retrospective study
Authors: Zhu Yiwan , Zhao Yucheng , Huang Yin , Xu Leilai , Xie Xiaohong 
Published: November 2023

Abstract
Background
With the development of novel anti-HER2 antibody-drug conjugates, the subgroup of breast cancer patients with low HER2 expression has attracted increasing interest. The aim of this study was to investigate the clinicopathological characteristics, molecular typing and survival prognosis of patients with HER2-low breast cancer.
Methods
This retrospective study involved the collection of 1023 cases of primary breast invasive ductal carcinoma patients who were diagnosed and treated at the Department of Breast Surgery of Zhejiang Provincial Hospital of Chinese Medicine between January 2016 and September 2021. Among them, 805 patients with HER2-negative breast cancer were included in the analysis. The aim of this study was to compare the clinicopathological characteristics, molecular typing, and survival prognosis between patients with HER2-low and HER2-zero breast cancer. The survival curves for disease-free survival (DFS) and breast cancer-specific survival (BCSS) were generated using the Kaplan-Meier method, and the log-rank test was applied to assess survival differences. Additionally, univariate and multivariate Cox proportional hazard regression models were used to analyze prognostic factors.
Results
Of the 805 patients with HER2-negative breast cancer, 515 (63.98%) had HER2 zero expression and 290 (36.02%) had HER2 low expression. HER2-low breast cancer patients accounts for 28.3% of all breast invasive ductal carcinoma, and the molecular typing was mainly Luminal B subtype. Compared with the HER2-zero group, the proportion of N stage 2 ~ 3 (P = 0.004), TNM stage 3 (P = 0.002) and HR positive status (P = 0.002) in the HER2-low group was higher. However, no significant difference was observed in DFS and BCSS between the two groups (P > 0.05). Among the 805 patients, 629 (78.1%) were HR positive and 176 (21.9%) were HR negative. Of the 629 HR-positive patients, 385 (61.2%) had HER2 zero expression and 244 (28.8%) had HER2 low expression. Compared with the HER2-zero group, the HER2-low group had a younger age at diagnosis (P = 0.031), a higher proportion of patients younger than 45 years (P = 0.003), and a higher incidence of N stage 2 ~ 3 (P = 0.001) and TNM stage 3 (P = 0.001). There was no significant difference in the DFS and BCSS between the two groups (P > 0.05). Among the 176 HR-negative patients, 130 (73.9%) had HER2 zero expression and 46 (26.1%) had HER2 low expression. Compared with the HER2-zero group, the patients in the HER2-low group were older at diagnosis (P = 0.047), and had a higher proportion of patients aged 45 or older (P = 0.036). Moreover, the HER2-low group had lower histological grade (P < 0.001) and Ki-67 proliferation index (P = 0.027). Nevertheless, DFS and BCSS did not significantly differ between the two groups (P > 0.05).
Conclusion
HER2-low breast cancer, which accounts for 28.3% of all breast invasive ductal carcinoma, has distinct clinicopathological characteristics and molecular typing. It appears that HR status plays a prominent role in determining the biological behavior of HER2-low breast cancer. Notably, no significant differences in survival prognosis were observed between HER2-low and HER2-zero breast cancer patients, regardless of HR status.