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The dynamics of HER2 status in esophageal adenocarcinoma
Aafke Creemers1,2, Eva A Ebbing1,2, Gerrit K J Hooijer3
1Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
Abstract:
Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome. Discordance, defined as any change in HER2 status between matched biopsy and post-neoadjuvant chemoradiation therapy resection specimen (N = 170), or between matched resection specimen and recurrence of patients not eligible for curative treatment (N = 61), was determined using the standardized HER2 status scoring system. Clinically relevant positive discordance was defined as a change to HER2 positive status, as this would imply eligibility for HER2-targeted therapy. A difference in HER2 status between biopsy and resection specimen and resection specimen and metachronous recurrence was observed in 2.1% (n = 3) and 3.3% (n = 2) of the paired cases, respectively. Clinically relevant discordance was detected in 1.4% (n = 2) of the resectable patients and 1.6% (n = 1) of the patients with recurrent disease. Patients with HER2-positive status tumors before start of neoadjuvant treatment showed better overall survival, but not statistically significant. No association between HER2 status discordance and survival was found. Clinically relevant HER2 status discordance was observed and in order to prevent under-treatment of patients, the assessment of HER2 status in the metastatic setting should preferably be performed on the most recently developed lesions if the previous HER2 assessment on archival material of the primary tumor was negative.
Insights
HER2 status can change in esophageal adenocarcinoma. Testing the most recent tumors is crucial for guiding HER2-targeted therapy and preventing under-treatment in patients with recurrent disease.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Diagnostics
Background:
- Trastuzumab is a standard therapy for HER2-overexpressing esophagogastric adenocarcinoma.
- HER2 status is typically assessed on primary tumor tissue, but may change during treatment or progression.
- Understanding HER2 status dynamics is critical for optimizing treatment strategies.
Purpose of the Study:
- To evaluate HER2 status changes in esophageal adenocarcinoma (EAC) in resectable and recurrent disease.
- To determine the clinical relevance and impact of HER2 status discordance on patient outcomes.
- To inform best practices for HER2 testing in EAC.
Main Methods:
- Analysis of paired tissue samples (biopsy vs. resection, resection vs. recurrence) from EAC patients.
- Standardized HER2 status scoring system applied to assess discordance.
- Evaluation of clinically relevant positive discordance (change to HER2 positive).
Main Results:
- HER2 status discordance was observed in 2.1% of biopsy-resection pairs and 3.3% of resection-recurrence pairs.
- Clinically relevant discordance occurred in 1.4% of resectable and 1.6% of recurrent cases.
- No significant association found between HER2 status discordance and patient survival.
Conclusions:
- HER2 status can be dynamic in esophageal adenocarcinoma.
- Clinically relevant HER2 status discordance necessitates re-evaluation, especially in recurrent disease.
- Testing HER2 on recent lesions is recommended if initial testing was negative to ensure eligibility for HER2-targeted therapies.
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