Gastric cancer is associated with substantial morbidity and mortality worldwide.
It is the second most common cause of cancer-related deaths globally.1
In the United States, the majority of patients with gastric cancer present
with advanced, metastatic, or inoperable disease, and typically require
HER2 as a therapeutic target
HER2 is a key driver of tumorigenesis. Its overexpression as a result
of HER2 gene amplification has been observed in a number of solid tumors.
The most notable of these is breast cancer, for which HER2 is now a well-established
therapeutic target for the drug Trastuzumab (Herceptin®).3 Testing for HER2 overexpression to identify breast cancer patients
who could benefit from
Herceptin® is now becoming the standard of care.4
Recent studies have demonstrated that HER2 is also an important biomarker
in gastric and gastro-esophageal junction (GEJ) adenocarcinomas. Analysis
of HER2 status by immunohistochemistry and in situ hybridization techniques
have shown that HER2 is overexpressed up to 34% of gastric tumors.5
Trastuzumab (Herceptin®) for Gastric Cancer Study (ToGA trial)
Results from the international, randomized, Phase III Trastuzumab for
Gastric cancer study (ToGA trial) demonstrated a clear survival benefit
from the addition of Trastuzumab (Herceptin®) to the therapy of those patients with advanced gastric or GEJ junction
adenocarcinoma that exhibits HER2 overexpression.6
Patients with high HER2-expressing tumors derived the greatest benefit
from trastuzumab therapy (Herceptin®). HER2 positivity can be established by immunohistochemistry and/or fluorescence
in situ hybridization (FISH).
On the basis of these findings, FDA approval for trastuzumab was granted
for patients with advanced gastric or GEJ junction adenocarcinoma when
HER2-positivity was determined using approved testing methods. Given that
the vast majority of patients with gastric/GEJ adenocarcinoma present
with advanced/metastatic disease (>70% based on the SEER data for gastric
cancer 2002-2008), a panel of experts recommended that “all patients
with gastric cancer should be tested for HER2 status at the time of
initial diagnosis, with
biopsies being the preferred specimen type due to specimen quality reasons.”7
Inform Diagnostics is excited to announce the initiation of a new testing
protocol that will aid in the management of patients with gastric and
GEJ adenocarcinoma. We will be performing HER2 testing by both IHC and
FISH on all patients with gastroesophageal adenocarcinomas (see figures 1 and 2).
Figure 1. Immunohistochemical stain for HER2 showing strong (3+) staining.
Figure 2. FISH for HER2/neu amplification.
We believe that your patients will benefit from this new test offering.
Inform Diagnostics plans to continue to be at the forefront of molecular
testing. And as always, we will only offer those tests that have clinical
value and scientific merit. You will be notified about additional tests
as they become available and as the scientific literature warrants. Please
call 866-588-3280 if you have any additional questions.
– Ahmed Bedeir, MD, GI Pathologist
- Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality,
and prevalence across five continents: defining priorities to reduce cancer
disparities in different geographic regions of the world. J Clin Oncol
2006; 24: 2137–50.
- Cunningham D, Allum WH, Stenning SP, et al for the MAGIC trial participants.
Perioperative chemotherapy versus surgery alone for resectable gastro-esophageal
cancer. N Engl J Med 2006; 355: 11–20.
- Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after
adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;
- Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal
antibody against HER2 for metastatic breast cancer that overexpresses
HER2. N Engl J Med 2001; 344: 783–92.
- Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for
gastric cancer: results from a validation study. Histopathology 2008;
- Bang Y-J, Van Cutsem E, Feyereislova A, et al for the ToGA trial investigators.
Trastuzumab in combination with chemotherapy versus chemotherapy alone
for treatment of HER2-positive advanced gastric or gastro-oesophageal
junction cancer (ToGA): a phase 3, open-label, randomised controlled trial.
Lancet 2010; 376: 687–97.
- Rüschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer:
a practical approach. Modern Pathology advance online publication 6 January
2012; doi: 0.1038/modpathol.2011.198.