Abstract:

Background and purpose: Human epidermal growth factor receptor 2 (HER2) is one of the main markers affecting the prognosis of breast cancer patients and the most important reference factor for the pathological classification of breast cancer. This study aimed to investigate the clinicopathological features of breast cancer with low expression of HER2 and its correlation with therapeutic effect and prognosis in neoadjuvant chemotherapy. Methods: The patients with HER2-negative breast cancer who received neoadjuvant chemotherapy in Fudan University Shanghai Cancer Center from 2009 to 2018 were retrospectively included. Clinicopathological information was collected, and the patients were divided into groups with low expression of HER2 (HER2-low) and no expression of HER2 (HER2-0), and their characteristic differences were analyzed. The independent influencing factors of pathological complete response (pCR) after neoadjuvant chemotherapy were evaluated by univariate and multifactorial methods, and the prognostic differences among different HER2 expression groups were evaluated by Kaplan-Meier curve. Results: In the 772 patients enrolled in this study, the proportion of HER2-low was significantly higher in hormonal receptor (HR) positive patients than in HR negative patients. Multivariate analysis of logistic regression model showed that tumor size (P<0.001), HR (P = 0.026) and HER2 expression (P = 0.018) were independent predictors of pCR. Subgroup analysis indicated that there was no significant difference in pCR rates between HER2-0 and HER2-low triple-negative breast cancer (TNBC) (P = 0.598). In Luminal breast cancer, the pCR rate of HER2-low patients was 9.4%, which was significantly lower compared with HER2-0 patients (19.3%, P = 0.003). In the survival analysis of non-pCR patients, the prognosis of HER2-low patients was significantly better compared with HER2-0 patients (P<0.001), and the 5-year survival rate was 72.2%, while the 5-year survival rate of HER2-0 patients was only 56.0%. Conclusion: HER2-negative patients with different expressions of HER2 protein have different clinicopathological characteristics, which are related to the chemotherapy sensitivity and prognosis of patients.

Key words: Human epidermal growth factor receptor 2, Breast cancer, Neoadjuvant chemotherapy, Pathological complete response, Prognosis