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

Background: 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. Methods: 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. Results: 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). Conclusions: 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. Registration: This meta-analysis was registered with PROSPERO (CRD42022335704) on June 10, 2022. Availability of data and materials: All data generated or analysed during this study are included in this published article [and its supplementary information files].

Automated summary

This study compared the survival outcomes of HER2-low and HER2-negative breast cancers and explored the impact of hormone receptor status. The results showed that HER2-low breast cancer had better survival outcomes than HER2-negative breast cancer in patients with early-stage breast cancer, regardless of hormone receptor status.