Comparative Prognosis of HER2-Low versus HER2-Negative Breast Cancer: A Meta-Analysis

With the emergence of new antibody-drug conjugates (ADCs), low human epidermal growth factor receptor (HER2) expression may become a novel treatment target. However, despite the clinical trials of new ADCs, strong evidence to prove the practical significance of HER2-low breast cancer (BC) prognosis remains unavailable. Methods: This systematic meta-analysis was undertaken to compare the prognostic value of the survival outcomes of patients with HER2-negative and HER2-low BC. For this, the Cochrane Library and PubMed were searched, and 23 eligible retrospective or prospective studies reporting information related to disease-free survival (DFS), overall survival (OS), and pathological complete response (PCR) rates of patients with HER2- negative and HER2-low BC were included. For both subgroups, the data were pooled using a random-effects model, with hazard ratios (HRs) for OS and DFS and odds ratios (ORs) for PCR, along with their 95% confidence intervals (CIs). OS was the primary endpoint, whereas DFS and PCR rates were the secondary endpoints. Results: We analyzed the 23 studies, which enrolled 781,941 patients with HER2-low BC. OS (HR = 0.82, 95% CI: 0.73-0.92, P = 0.001) significantly improved in patients with HER2-low BC compared with those with HER2-negative BC. However, DFS (HR = 0.87, 95% CI: 0.67-1.12, P = 0.28) did not significantly improve. Furthermore, the PCR rate was lower in patients with HER2-low BC than in patients with HER2-negative BC (OR = 0.88, 95% CI: 0.83-0.93, P < 0.001). Conclusion: Compared with the HER2-negative status, OS is significantly increased, and PCR is significantly decreased in the HER2-low status. However, DFS is not significantly increased.