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Survival Outcomes in ERBB2-Low vs ERBB2-Null Advanced Gastric Cancer
Beliz Bahar Karaoglan1,2,3, Eduardo Terán4, Pau Mascaró Baselga4
1Department of Medical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey.
JAMA Network Open
|July 21, 2026
Summary
ERBB2-low gastric cancer (GC) patients showed worse survival outcomes compared to ERBB2-null GC. However, ERBB2 status alone is not an independent predictor of survival in advanced GC.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- ERBB2 (formerly HER2)-low gastric cancer (GC) is gaining attention with new targeted therapies.
- The clinicopathologic features and prognostic significance of ERBB2-low GC compared to ERBB2-null GC remain unclear.
Purpose of the Study:
- To compare clinicopathologic characteristics of ERBB2-low and ERBB2-null advanced GC.
- To assess if ERBB2 status independently impacts survival outcomes in advanced GC.
Main Methods:
- International, multicenter retrospective cohort study of advanced metastatic GC patients.
- ERBB2 expression categorized as ERBB2-low (IHC 1+ or IHC 2+/ISH-) or ERBB2-null (IHC 0).
- Progression-free survival (PFS) and overall survival (OS) analyzed using Cox regression models.
Main Results:
- ERBB2-low GC patients were older, more often male, and had worse ECOG performance status.
- Liver metastases and elevated CEA levels were more common in the ERBB2-low group.
- Median PFS and OS were shorter for ERBB2-low GC compared to ERBB2-null GC (PFS HR 1.36, P=.003; OS HR 1.34, P=.006).
Conclusions:
- ERBB2-low advanced GC is associated with inferior survival compared to ERBB2-null GC.
- ERBB2 status was not an independent predictor of survival, suggesting baseline clinical factors drive survival differences.
- ERBB2-low status alone may be insufficient for prognostic stratification in advanced GC.
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