<i>HER2</i> Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology

TLDR

HER2 is the only biomarker used to select therapy for advanced gastroesophageal adenocarcinoma, yet no comprehensive testing guidelines exist. The authors aim to establish an evidence‑based guideline for HER2 testing in GEA, defining optimal testing algorithms, specimen selection, and clinical decision‑making. An expert panel from CAP, ASCP, and ASCO performed a systematic literature review to develop recommendations for accurate HER2 assessment in GEA. The panel issued 11 strongly agreed recommendations, including mandatory HER2 testing before therapy, recommending upfront combination chemo plus HER2‑targeted agents for HER2‑positive patients, and providing detailed pathologist guidance on tissue selection, testing, scoring, reporting, and quality assurance.

Abstract

Context ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. Objectives To establish an evidence-based guideline for HER2 testing in patients with GEA, formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making. Design The College of American Pathologists (CAP), American Society for Clinical Pathology (ASCP), and the American Society of Clinical Oncology (ASCO) convened an Expert Panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA. Results The Panel is proposing 11 recommendations with strong agreement from the open comment participants. Recommendations The Panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and an HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance. Conclusion This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results.