Prognostic Impact and Clinicopathological Correlates of HER2 Status in Gastric Cancer: A Multicenter Retrospective Turkish Oncology Group Study


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Yildirim S., Sever O. N., Turkoglu E., Sariyar Busery N., Dogan A., Baydas T., ...Daha Fazla

CLINICAL MEDICINE INSIGHTS: ONCOLOGY, cilt.20, ss.1-23, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1177/11795549261445290
  • Dergi Adı: CLINICAL MEDICINE INSIGHTS: ONCOLOGY
  • Derginin Tarandığı İndeksler: Scopus, Science Citation Index Expanded (SCI-EXPANDED), CINAHL, EMBASE, Directory of Open Access Journals
  • Sayfa Sayıları: ss.1-23
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Background: Gastric cancer remains one of the most common malignancies and a leading cause of cancer-related mortality worldwide. Human epidermal growth factor receptor 2 (HER2) status is a key biomarker influencing both prognosis and treatment selection. While HER2-positive patients benefit from trastuzumab, outcomes for HER2-low and HER2-zero groups remain less clearly defined. Methods: In this retrospective cohort study, we reviewed 507 patients diagnosed with metastatic gastric adenocarcinoma between 2015 and 2023. Patients were classified as HER2-zero (n = 134), HER2-low (n = 303), or HER2-positive (n = 70) based on immunohistochemistry and in situ hybridization results. Clinicopathologic features, treatment strategies, and survival outcomes were analyzed. Kaplan-Meier methods estimated progression-free survival (PFS) and overall survival (OS), whereas Cox regression identified independent prognostic factors. Results: The HER2-positive group achieved a median PFS of 9.0 months and OS of 20.0 months, superior to HER2-zero patients (PFS: 6.1; OS: 14.5; P  < .001). HER2-low patients demonstrated intermediate outcomes (PFS: 6.7; OS: 16.6 months). Group distribution was HER2-zero 26.4%, HER2-low 59.8%, and HER2-positive 13.8%. All HER2-positive patients received trastuzumab-based therapy. Multivariate analysis confirmed HER2-positive status as an independent predictive factor for both progression (hazard ratio [HR] = 0.65) and mortality (HR = 0.62). Conclusions: HER2 status is a strong predictive determinant in metastatic gastric cancer. Trastuzumab provided significant real-world benefit for HER2-positive patients, validating the impact of targeted therapy. Notably, HER2-low patients had better outcomes than HER2-zero, supporting the recognition of HER2-low as a distinct subgroup with potential eligibility for future HER2-directed treatments.