The dynamics of HER2 status in esophageal adenocarcinoma
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Aafke Creemers1,2, Eva A. Ebbing1,2, Gerrit K.J. Hooijer3, Lisanne Stap2, Rajni A. Jibodh-Mulder1, Susanne S. Gisbertz4, Mark I. van Berge Henegouwen4, Maurits L. van Montfoort3, Maarten C.C.M. Hulshof5, Kausilia K. Krishnadath6, Martijn G.H. van Oijen2, Maarten F. Bijlsma1, Sybren L. Meijer3 and Hanneke W.M. van Laarhoven1,2
1Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands
2Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands
3Department of Pathology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands
4Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands
5Department of Radiotherapy, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands
6Department of Gastroenterology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands
Aafke Creemers, email: [email protected]
Keywords: HER2; esophageal adenocarcinoma; dynamics; neoadjuvant therapy
Received: February 03, 2018 Accepted: May 14, 2018 Published: June 01, 2018
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.
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