Evolution and clinical significance of HER2-low status after neoadjuvant therapy for breast cancer

BACKGROUND: The emergence of HER2 antibody-drug conjugates provides new treatment decisions for breast cancer patients, especially those with HER2-low expression. In order to explore the biological characteristics of breast cancer with HER2-low expression, the HER2-low category in primary breast cancer and residual tumor after neoadjuvant therapy was investigated to reflect the evolution of HER2 expression. METHODS: HER2 was assessed according to the latest ASCO/CAP guidelines. The cut-off value for staining of HER2-positive cells was >10%. HER2-negative cases were divided into HER2-low (IHC=1+/2+ and no ISH amplification) and HER2-zero (IHC-0), and the clinicopathological characteristics of the cases were collected. RESULTS: This study included 1140 patients with invasive breast cancer who received preoperative neoadjuvant therapy from 2018 to 2021, of which 365 patients achieved pCR and 775 were non-pCR. In the non-pCR cohort, HER2-low cases accounted for 59.61% of primary tumors and 55.36% of residual tumors. Among HER2-negative cases, HR-positive tumors had a higher incidence of low HER2 expression compared with triple-negative tumors (80.27% vs 60.00% in primary tumors and 72.68% vs 50.77% in residual tumors). The inconsistency rate of HER2 expression was 21.42%, mainly manifested as the conversion of HER2-low cases to HER2-zero (10.19%) and the conversion of HER2-zero to HER2-low (6.45%). Among the HER2-negative cases in the primary tumor, the HER2 discordance rate of HR-positive cases was lower than that of triple-negative cases (23.34% VS 36.92%). This difference was mainly caused by the case switching from HER2-low to HER2-zero. Compared with HER2-zero cases, there were statistically significant differences in RCB grade, MP grade and the number of metastatic lymph nodes in HER2-low cases. Patients with low HER2 expression had a lower pathological response rate and a higher number of metastatic lymph nodes. CONCLUSION: HER2-low breast cancer is highly unstable during disease evolution and has certain biological characteristics. HER2-low breast cancer is not only correlated with positive HR, but also has a certain correlation with positive AR. Re-detection of HER2 in breast cancer after neoadjuvant therapy may lead to new treatment opportunities for a certain proportion of patients.