HER2 epidermal growth factor receptor, tests used to look for its amplification in breast cancer: Principles and limitations

HER2-positive breast cancer accounts for 20 % of all invasive breast cancers. It is associated with increased recurrence, a higher risk of brain metastases and a shorter overall survival than luminal A and B cancers. The presence of ERBB2 gene amplification is predictive of a good response to anti-HER2 therapies. Determining HER2 status is a hot topic, given recent studies on HER2-low subtypes. Although several techniques are available, the latest 2018 update from the American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) recommends a first immunohistochemical study followed by a fluorescence in situ hybridisation study indicated only for equivocal cases. This article summarises the different techniques used to determine HER2 status and provides a detailed review of the literature on pre-analytical factors and intrinsic tumour-specific factors that can distort or complicate the interpretation of results.