Overview of recommendations of HER2 testing in breast cancer

HER2 overexpression is present in approximately 15% of invasive breast cancers, and is an important prognostic and predictive marker. HER2 status should be determined in all newly diagnosed breast cancers, and testing involves immunohistochemistry looking for protein overexpression and/or fluorescence in-situ hybridization (FISH) to detect the presence of HER2 gene amplification. Both techniques can be performed on formalin-fixed, paraffin-embedded tissue. Each has limitations, and preanalytical factors, such as fixation, can impact the accuracy of results. FISH is more reproducible than immunohistochemistry, and shows a stronger correlation with response to HER2-targeted therapies. However, it is more expensive and requires specialized fluorescence microscopy, so immunohistochemistry remains the frontline test in most current algorithms. Chromagenic in-situ hybridization (CISH) is an alternative to FISH and uses a chromagen-based signal detectable by bright field microscopy, making it more assessable to routine diagnostic pathology laboratories. Whichever technique is used, strict quality control and external quality assurance are essential.