Comparison of the Pathological Complete Response Rate and Survival between HER2-low and HER2-zero Breast Cancer in Neoadjuvant Chemotherapy Setting: a Systematic Review and Meta-analysis

Although HER2-low breast cancer (BC) constitutes almost 50% of all BC types, its impact on the pathological complete response (pCR) rate and survival in early BC is uncertain. As a result, a systematic review was conducted to compare the pCR rate and survival of HER2-low and HER2-zero BC in the neoadjuvant chemotherapy (NACT) setting. Two reviewers independently performed literature searches using EMBASE, PubMed, and Cochrane Libraries internet databases up to June 2023. Finally, 29 studies with 178,294 patients were included. HER2-low BC had a considerably lower pCR rate compared to HER2-zero BC in the entire population (Risk Ratio (RR) = 0.68, p < 0.001) and in the hormone receptor (HR)-positive subgroup (RR = 0.73, p = 0.009), but not in the HR-negative subgroup (RR = 0.99, p = 0.755). Furthermore, patients with HER2-low BC exhibited prolonged disease-free survival (DFS) and overall survival (OS) compared to those with HER2-zero BC, observed in both the entire cohort (DFS: p = 0.004; OS: p = 0.008) and the HR-negative subgroup (DFS: p = 0.009; OS: p < 0.001). In the HR-positive population, OS was superior in HER2-low BC patients (p < 0.001), whereas no significant differences in DFS were observed (p = 0.064). Our findings imply that the pCR rate and prognosis of HER2-low BC are distinguished from those of HER2-zero BC in early BC treated with NACT, which contributes to a better knowledge of the BC subgroup.