Answer: Today, there are two acceptable ways of testing for HER2 drive in a breast cancer patient: Immunohistochemistry [IHC], which tests for overexpression of the protein; or FISH [fluorescence in situ hybridization] testing, which tests for gene amplification—you're supposed to have two copies of the HER2 gene, whereas many overexpressed or amplified tumors have multiple copies of the HER2 gene (Carlson RW et al. J Natl Compr Canc Netw. 20064(suppl 3):S1-22; Hammond ME et al. J Clin Oncol. 2010;28:2784-2795. doi:10.1200/JCO.2009.25.6529; Summary of ASCO/CAP HER2 Guideline Recommendations http://www.cap.org/apps/docs/committees/immunohistochemistry/summary_of_recommendations.pdf. Accessed March 28, 2013).
When the test results are quite clear [that] either the HER2 FISH test is amplified or the HER2 immunohistochemistry is overexpressing, then clinical decision-making is relatively easy. We know that both in the early stage and metastatic setting, women who have amplification or overexpression of the HER2 gene benefit from HER2-targeted therapies.In about 1% to 2% of newly diagnosed breast cancer patients, however, the HER2 testing is equivocal. That means not negative or not positive, but unclear what the benefit of HER2 treatment would be, so many patients and clinicians find themselves in a difficult situation. In that case, we always recommend HER2 FISH testing to try to clarify exactly how HER2-driven the breast cancer is (Wolff AC et al. J Clin Oncol. 2007;25:118-145; College of American Pathologists. HER2 Testing Guidelines and Resources [Updated April 18, 2011]. http://www.goo.gl/96Gnl. Accessed April 12, 2013). A dialogue between you, as a clinician, and your clinical pathologist becomes critical in these situations where the testing is equivocal. And in fact, knowing who the pathologist [is] and even making certain that the sample that they're looking at helps them with the testing is critical in clinical decision-making surrounding HER2-positive newly diagnosed breast cancer.