Survival differences between HER2-0 and HER2-low-expressing breast cancer − A meta-analysis of early breast cancer patients

HER2-low (human epidermal growth factor receptor 2) breast cancer takes up 40–50% in all breast cancer subtypes. The survival difference between HER2-low and HER2-zero breast cancers remain uncertain. Therefore, the aim of this study was to compare survival outcome of the two subtypes and to explore the impact of hormone receptor status. A comprehensive medical literature search was performed by searching PubMed, EMBASE, and the Cochrane Libraries up to August 2022. We included observational studies reporting hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). The results of individual studies were pooled by random-effects models using Stata 16.0. Seventeen articles with a total of 78984 breast cancer patients were included in the meta-analysis. We observed a statistically significant association between low HER2 expression and better breast cancer survival outcomes (OS: HR: 0.83; 95% confidence interval: 0.75, 0.90; DFS/RFS: HR: 0.83; 95% confidence interval: 0.75, 0.91). In a subgroup analysis, we found that HER2-low patients had better survival outcomes relative to hormone receptor-positive breast cancer patients (OS: HR: 0.87; 95% confidence interval: 0.81, 0.93; DFS/RFS: HR: 0.91; 95% confidence interval: 0.85, 0.96). Similarly, in triple-negative breast cancer patients, we also observed a positive association between HER2 low expression and better survival (OS: HR: 0.85; 95% confidence interval: 0.71, 0.98; DFS/RFS: HR: 0.85; 95% confidence interval: 0.74, 0.95). Our study showed that HER2-low breast cancer had better survival outcomes compared to HER2 negative breast cancer in patients with early stage breast cancer, regardless of hormone receptor status. This meta-analysis was registered with PROSPERO (CRD42022335704) on June 10, 2022. All data generated or analysed during this study are included in this published article [and its supplementary information files]. •In the overall population, we found that patients with low HER2 expression breast cancer had better overall survival than patients with HER2 zero breast cancer.•Similarly, the survival advantage of disease-free survival or recurrence free survival can be demonstrated in hormone receptor positive and negative population cohorts.