Dynamics of the HER2 receptor in esophageal adenocarcinoma: New opportunities for targeted therapy

Background

Trastuzumab, a monoclonal antibody directed against HER2, has become standard of care for metastatic HER2 overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment in esophageal adenocarcinoma (EAC). In clinical practice HER2 overexpression is usually determined on archived tumor material, from primary tumor biopsies or resection specimens. However, HER2 overexpression may change in the course of treatment or disease progression. The aim of this study was to assess the dynamics and clinical implications of HER2 expression in both curative and palliative setting.

Methods

Matched biopsies and resection specimens of 108 EAC patients treated with neoadjuvant chemoradiation, and 68 EAC resection specimens and matched biopsies of metachronous distant metastases were collected. All samples and specimens were simultaneously stained for HER2 on an automated immunostainer using the anti-HER-2/c-erB-2/neu (clone SP3) antibody. Discordance, either up- or downregulated HER2 expression between biopsy and resection specimen or resection specimen and metastases, was determined using the standardized HER2 expression scoring system by Hofmann et al. (Hofmann, Stoss et al. 2008).

Results

HER2 overexpression (immunohistochemistry scores 2+ and 3+) was detected in 14.8% of the pre-treatment biopsies and 14.2% of the neoadjuvantly treated resection specimens. A significant discordance between biopsy and resection specimen (p 

Conclusions

HER2 overexpression is observed in 14% of the primary EAC biopsies, with significant dynamics in HER2 expression between pre-treatment biopsy and neoadjuvantly treated resection specimen. Remarkably, only 3% discordance was observed between resection specimen and metachronous distant metastases. Therefore, the assessment of HER2 expression in the metastatic setting should preferably be performed on the most recent acquired material, but HER2 determination on resection material may also be valid.

Clinical trial identification

Legal entity responsible for the study

AMC

Funding

AMC

Disclosure

H.W.M. van Laarhoven: Consultant: Nordic, Lilly. Research funding: Bayer, Cell Gene, MSD, Roche, Nordic, Lilly, Janssen- Cilag, GSK. All other authors have declared no conflicts of interest.