: Metastatic gastric cancer (GC) is an extremely fatal malignant disease. Human epidermal growth factor receptor 2 (HER2) is an important therapeutic target in patients with HER2 overexpression or gene amplification. However, the prognostic value of HER2-low expression is still controversial. This study aims to investigate the effect of HER2 expression levels on clinicopathological characteristics and clinical outcomes in patients with metastatic GC.

: The study included patients who had diagnosed de novo or recurrent metastatic GC from January 2011 to January 2023. We classified the patients into three categories based on their HER2 expression level: negative, low, and positive.

: The current study included 191 patients, with 99 (51.8%) classified as HER2-negative, 42 (22.2%) as HER2-low, and 50 (26.2%) as HER2-positive. There were significant differences in the primary origin of gastroesophageal junction (25.3%, 23.8%, and 44%), signet ring cell carcinoma (54.8%, 44.4%, and 16%), mucinous cell carcinoma (40.9%, 27.8%, and 12%), intestinal type histology (17.9%, 50%, and 48.9%), high carcinoembryonic antigen level (34.5%, 46.2%, and 56.5%), >2 metastatic sites (25.3%, 45.2%, and 42%), liver metastasis (33.3%, 42.9%, and 66%), peritoneal metastasis (44.4%, 28.6%, and 20%), and distant lymph node metastasis (53.5%, 83.3%, and 58%) among the HER2-negative, HER2-low, and HER2-positive groups, respectively. The HER2-low group had similar median overall survival (OS) compared to the HER2-negative group (14.8 vs. 14.5 months, p = 0.868), however, significantly shorter median OS than the HER2-positive group (14.8 vs. 18.6 months, p = 0.024).

: Our findings demonstrated that patients with HER2-low metastatic GC had different clinical and pathological features. The poorer survival rates of the HER2-low group compared to the HER2-positive group might be due to the lack of effective targeted treatments for HER2-low disease. Further research is warranted to develop specific therapeutic strategies for this subgroup.