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Discordance in HER2 Status in Gastro-esophageal Adenocarcinomas: A Systematic Review and Meta-analysis

A Creemers1,2, E Ter Veer3, L de Waal3

  • 1Cancer Center Amsterdam, Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.creemers@amc.uva.nl.

Scientific Reports
|June 11, 2017
PubMed

Insights

A strict definition for human epidermal growth factor receptor 2 (HER2) positivity reduces discordance between primary tumors and metastases in gastro-esophageal cancers. This improves patient selection for HER2-targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Trastuzumab plus chemotherapy is standard for HER2-positive advanced gastro-esophageal cancers.
  • HER2 discordance between primary tumors and metastases complicates patient selection for targeted therapy.

Purpose of the Study:

  • To explore how HER2 assessment methods influence discordance rates.
  • To investigate the prevalence of HER2 discordance in gastro-esophageal adenocarcinomas.

Main Methods:

  • Systematic literature search of PubMed, Embase, and Cochrane databases (until January 2016).
  • Random-effect meta-analyses to compare discordance rates between strict and broad HER2 definitions.
  • Random-effect single-arm meta-analyses to assess overall HER2 discordance and conversion rates.

Main Results:

  • A strict HER2 definition significantly lowered discordance rates (RR=0.58) compared to broader definitions (6.2% vs. 12.2% pooled discordance).
  • Overall pooled discordance using the strict definition was 7% (95% CI 5-10%).
  • Lowest discordance observed with strict HER2 positivity assessment.

Conclusions:

  • Strict HER2 assessment methods minimize discordance between primary tumors and metastases.
  • Standardizing patient selection for HER2-targeted therapy using a strict definition enhances comparability of treatment outcomes across studies.

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