Gastric adenocarcinoma is a major cause of morbidity and mortality in the world with median overall survival being less than
a year. Advanced gastric adenocarcinoma is associated with a dismal prognosis, and increasing survival time, even by a few months,
can be significant in this patient population. Recently there was a major breakthrough in the treatment of gastric cancer, which arose by
studying a therapy currently used for treatment of another solid tumor,HER2 positive breast carcinoma. Trastuzumab, a monoclonal antibody
that targets the extracellular domain of the HER2 receptor, has become standard first-line treatment in this classification of breast carcinomas. A recent clinical trial (ToGA) using trastuzumab in combination
with chemotherapy versus chemotherapy alone for treatment of HER2- positive advanced gastric or gastro-esophageal junction cancer showed
an increase in overall survival in advanced (inoperable locally advanced, recurrent, or metastatic) gastric cancer treated with chemotherapy
plus trastuzumab versus chemotherapy alone. This was the first time a biological therapeutic was proven to increase survival in gastric
cancer. Critical to the ToGA trial was determining which patients would be eligible for randomization - i.e. which patients had tumors
that over-expressed HER2. Therefore, not only was trastuzumab shown to prolong survival in patients with advanced gastric cancer,
but a protocol was proposed for HER2 testing in gastric cancer in a corollary study. HER2 interpretation in gastric cancer is similar to,
but slightly different than interpretation in breast cancer. Hofmann put forth an initial proposal, which was subsequently validated with minor
clarifications added by Ruschoff.
Last date updated on September, 2024