Incorporation of a new biological marker such as HER2 into routine clinical practice requires proof that it provides reproducible information independent of, and better than, conventional pathologic criteria, and that it influences treatment decisions. In breast cancer, HER2 amplification/overexpression predicts for a poor clinical outcome and an enhanced survival benefit from the HER2-targeted therapy, Herceptin®, and may predict for resistance to some conventional therapies. Thus, HER2 is considered to be a clinically important molecule and testing for HER2 abnormalities is already part of routine patient assessment in many parts of the world. There is currently no gold standard for HER2 testing. The main challenge is to standardize and technically validate HER2 testing methodologies. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the most common HER2 tests used, and show a high level of concordance. HER2 testing approaches based on the polymerase chain reaction (PCR) are under extensive investigation and appear promising. A Canadian HER2 testing algorithm designed to increase the validity and reproducibility of HER2 testing has been compiled. HER2-positive cases are defined as those with >10% of tumor cells with moderate/strong, complete membrane staining in the invasive component, by IHC. Confirmatory HER2 testing using either FISH or quantitative PCR is recommended for indeterminate cases. Additional studies are required to calibrate HER2 testing results to clinical outcome.

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