Standardized Assessment of the HER2 Status in Breast Cancer by Immunohistochemistry

Immunohistochemistry (IHC) is widely used in surgical pathology, but it has been plagued by problems with reproducibility and lack of standardization resulting in poor concordance between laboratories. In particular, inaccuracy of routine human epidermal growth factor receptor 2 (HER2) testing in breast cancer patients has been a major issue. In 2006 this led the American Society of Clinical Oncologists (ASCO) and College of American Pathologists (CAP) to charge an expert panel with developing recommendations for HER2 testing. After subsequent publication and adoption of these guideline recommendations through dissemination of best practices, variation in clinical practice is expected to diminish and result in improved accuracy. In this article, we review the role of genomic HER2 alterations in the development and treatment of breast cancer, highlight the importance of accurate and reproducible HER2 testing, and discuss practical approaches to standardize HER2 testing by IHC. Pre-analytic and analytic variables are addressed, and a practical algorithm for test interpretation is introduced.