Say the words “HER2 gene amplification” and what immediately comes to mind is breast cancer. But did you know other cancers, including those of the stomach and esophagus (collectively called gastroesophagel adenocarinoma or GEA) can have too many (> 6) copies of the HER2 gene? That’s right, an estimated 20% of GEA cancers harbor an amplified HER2 gene biomarker, and these tumors are predicted to behave aggressively just like their breast cancer counterparts. The good news is HER2 gene amplification is now considered a “druggable target” in GEA cancer and the same drug used to combat HER2 positive breast cancer is also FDA approved for HER2 positive gastric cancer.
So how to find the 20% of GEA cancers with amplified HER2 genes? It turns out we can enlist the same clinical laboratory testing methods already in use for identification of HER2 positive breast cancer. Since 2010 when trastuzumab (Herceptin®, made by Genentech, Inc.) was FDA approved for gastric cancer, a percentage of these tumors began to be evaluated by pathologists for HER2 positivity. Yet until recently, many pathologists were still not routinely incorporating HER2 testing into the diagnostic workup of all GEA cancers. This is most likely because the HER2 testing guidelines published in 2007 and updated in 2013 by the College of American Pathologists (CAP) and American Society of Clinical Oncology (ASCO) for breast cancer did not include gastric cancer. So although the clinical tests were the same, how to perform and interpret these tests for gastric versus breast cancer has not been clear.
Guidance for pathologists traversing the galaxy of HER2 testing in gastric cancer arrived on November 16, 2016 with the publication of CAP/ASCO guidelines specifically for GEA tumors. Prepared by an Expert Panel, the 21-page document contains a list of strong recommendations for accurate determination of HER2 status in GEA tumor issue. All patients with advanced GEA who are eligible for systemic therapy should have their tumor tissue tested for HER2 positivity. The GEA HER2 testing guidelines can be freely accessed and are available through the following link: http://ascopubs.org/doi/pdf/10.1200/JCO.2016.69.4836. According to the guidelines, testing should begin at the protein level with analysis of the HER2 receptor drug target on the surface of the tumor cells. If the protein does not provide an actionable answer, then the HER2 gene copy number on chromosome 17 is tested for amplification. In cases where neither of these tests provide clarification as to how the patient should be treated, novel more accurate methods such as DNA microarray analysis may be considered.
In patients with GEA cancer, tumors harboring HER2 gene amplifications will only be found if pathologists look for them. The CAP/ASCO guidelines bring new hope for the galaxy of GEA tumor testing and move the field closer to a day when HER2 testing is a routine part of the diagnostic workup of every patient’s tumor tissue.
Shelly Gunn MD, PhD| Pathologist| January 24, 2017