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tric/esophagogastric junction adenocarcinoma [ 11 ]. Trastuzumab
has emerged as a novel treatment option for patients with HER2-
positive advanced gastric/esophagogastric junction carcinoma,
approved by the Food and Drug Administration (FDA) in the
USA, Therapeutic Goods Administration (TGA) in Australia, and
similar government and professional bodies.
HER2 overexpression correlates with tumor invasion and
lymph node metastasis, and thus indicates a poor prognosis [ 12 –
14 ]. The data on HER2 overexpression in esophageal adenocarci-
noma are variable. The differences among reported overexpression
rate might depend on stage of the disease, ethnicity, geography,
methodology of testing, and interpretation of results. Studies that
specifically analyzed HER2 expression and/or amplification in
Barrett esophagus reported positivity rates of 38–50% and showed
an association with progression from Barrett’s esophagus to dys-
plasia and adenocarcinoma [ 15 – 18 ]. A very small pilot study
showed that trastuzumab treatment caused HER2 down regula-
tion and increased apoptosis in patients with dysplasia and adeno-
carcinoma arising in Barrett esophagus [ 19 ]. Understanding the
role and prevalence of biomarkers such as human epidermal growth
factor receptor 2 (HER2) may possibly shed more light on the
progression of Barrett esophagus to dysplasia and ultimately to
adenocarcinoma. Currently, a phase III trial study investigating the
effect of radiation therapy, paclitaxel, and carboplatin with or with-
out trastuzumab for patients with esophageal cancer is underway
[(The Radiation Therapy Oncology Group (RTOG) 1010 trial
(NCT01196390)].
Overall, accurate determination of the HER2 status is crucial
to ensure selection of the correct patient who may benefit from the
target therapy for esophageal adenocarcinoma. The information is
influenced by the experience of testing in esophagogastric junction
cancer in the ToGA trials and subsequent studies.2 Materials
As the benefit of the anti-HER2 monoclonal antibody (trastu-
zumab) is limited to patients with HER-2 overexpression and gene
amplification, careful selection of patients is crucial to avoid unnec-
essary treatment for those who are not eligible. HER2 positivity
determines the eligibility for HER2 targeted therapy of advanced
and metastatic esophageal adenocarcinomas. The eligible patients
are whose tumor is HER2 positive. HER2 status can be deter-
mined by estimation of protein expression by immunohistochem-
istry (IHC) and assessment of HER2 amplification by in situ
hybridization (ISH).2.1 Selection
of Patients
for Potential Targeted
Therapy
Duminda Subasinghe et al.