HER2 testing: laboratory, technical and clinical considerations

HER2 measurement holds great promise in predicting response to a variety of systemic therapies an exciting step forward in the management of breast cancer patients. The enthusiasm surrounding the clinical importance of HER2, however, is tempered by the uncertainty regarding the clinical usefulness and accuracy of the different methodologies currently available to assess HER2 status. In this paper the authors address laboratory and technical issues associated with methods which measure HER2 overexpression or amplification. We also discuss how these issues can influence the clinical utility and routine application of this marker. While a tumor marker may be considered clinically relevant, it must be proven to be clinically useful. Optimally, this should occur in the setting of a randomized clinical trial, using methods that are reliable, reproducible, and biologically accurate. For HER2 testing to be a useful, routine clinical marker several critical issues need to addressed. These include the determination and validation of the clinical utility of each method to predict response to the different systemic therapies currently associated with HER2. In addition, there is need to set standards for assay performance and interpretation of assay results, based on criteria that are clinically validated.