Abstract Background Human epidermal growth factor receptor 2 (HER2) is a key oncogene implicated in several cancers, including breast cancer, gastric cancer, and adenocarcinoma of the esophagogastric junction (AEG). While HER2-positive tumors benefit from established therapies like trastuzumab, the clinical significance of HER2-low expression (IHC 1+ or 2+/ISH-negative) is less well understood, particularly in AEG. Studies in breast and gastric cancer suggest that HER2-low tumors may represent a less aggressive subtype with improved overall survival (OS). This study aims to investigate the impact of HER2-low expression on prognosis and clinicopathological features in HER2-non-amplified AEG patients. Methods This retrospective study analyzed 74 HER2-non-amplified AEG patients who underwent surgery without neoadjuvant therapies. HER2 status was assessed using IHC and ISH, and cases were reclassified as HER2-null (IHC 0) or HER2-low (IHC 1+ or 2+/ISH-negative). Clinicopathological features, disease-free survival (DFS), and overall survival (OS) were compared between groups. Kaplan–Meier survival analysis and Cox proportional hazards models were used to assess prognostic factors, with significance set at p 0.05. Results HER2-low expression was observed in 27% of patients. The HER2-low group had a higher proportion of well-to-moderately differentiated tumors (p = 0.04). Although no significant differences in DFS were found, OS was significantly longer in the HER2-low group (p = 0.01). Among patients with Stage III–IV disease, the HER2-low group had better OS (p = 0.04). Post-recurrence chemotherapy response was superior in the HER2-low group, with a complete response rate of 50% compared to 0% in the HER2-null group (p = 0.03). Conclusion HER2-low expression in AEG is associated with better OS, likely due to enhanced chemotherapy responses. While HER2-low status was not an independent prognostic factor, its correlation with improved treatment outcomes underscores its potential as a therapeutic target. Future studies are needed to validate these findings and explore HER2-low-targeted therapies to optimize treatment strategies for AEG patients.
Gokon et al. (Fri,) studied this question.