Prognosis difference between HER2-low and HER2-zero breast cancer patients: a systematic review and meta-analysis

HER2-low breast cancer (BC) is proposed to be a special population of patients with an immunohistochemistry (IHC) score of 1 + or 2 + and non-amplified in situ hybridization (ISH) results. The role and prognostic impact of HER2-low BC is still controversial. This meta-analysis aims to explore the prognostic difference between of HER2-low and HER2-zero characteristic in BC patients.

A meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and eligible studies were search in PubMed, Web of Science and EMBASE databases. Quality assessment of included studies were performed by Quality in Prognostic Studies (QUIPS) tool. Hazard ratios (HRs) and corresponding 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS) were pooled in a meta-analysis. Furthermore, subgroup analysis, sensitivity analysis, and analysis for publication bias were conducted.

Eighteen studies comprising a total of 93,317 patients were included for meta-analysis. BC patients with HER2-low characteristic have longer OS (HRs 0.87, 95% CI 0.81-0.93, p < 0.0001) and DFS (HRs 0.82, 95% CI 0.73-0.93, p = 0.001) compared to those with HER2-zero characteristic. Subgroup analysis indicate that the source of heterogeneity may come from the hormone receptor (HR) status group. Although, the publication bias was detected, sensitivity analysis and the trim-and-fill method analysis demonstrated the stability and reliability of the results.

HER2-low BC patients have longer OS and DFS compared to HER2-zero BC patients, and its prognostic value is consistent among different HR status patients. Whether HER2-low breast cancer is an independent subtype of breast cancer is still a subject of ongoing research, and more studies are needed to fully understand the molecular and clinical features of this subtype.