Introduction: Testing for human epidermal growth factor receptor-2 in breast cancer at the time of primary diagnosis is now the standard of care. Positivity for epidermal growth factor receptor-2 in breast cancer is a prognostic factor regarding tumor aggressiveness and a predictive factor for response to Herceptin. Accurate assessment is essential to ensure that all patients who may benefit from Herceptin are correctly identified.
Assay method: The principal testing methods used for determination of epidermal growth factor receptor-2 status are immunohistochemistry for protein overexpression and in situ hybridization using either fluorescence or a chromogen. Immunohistochemical testing method allows identification of epidermal growth factor receptor-2 positive patients (3+) who may benefit from Herceptin therapy, whereas negative patients (0/1+) can be excluded. A proportion of specimens defined as equivocal by immunohistochemistry (2+) must be retested by in situ hybridization to determine their status. Chromogen in situ hybridization is a method for determination of gene amplification using a peroxidase-based chromogenic reaction, which can be viewed using a conventional bright field microscope and it determines the actual degree of gene amplification. Various factors can affect the results achieved with these assays, including the assay antibody/probe, the methodology and the experience of personnel. Many countries implemented national testing guidelines in an attempt to standardize testing procedures and make results more accurate.
Conclusion: The key point underlined by this review is that whatever method is used to test HER2 status, the technology must be validated first, and there must be regular internal and external quality assurance procedures.