HER2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update Summary

First released in 2007 and updated in 2013, the recommendations by the ASCO/College of American Pathologists Human Epidermal Growth Factor Receptor 2 (HER2) Testing Expert Panel were developed to set standards to improve the performance and clinical utility of testing for HER2 as a predictive biomarker for potential responsiveness to therapies targeting the HER2 protein.1-4 HER2 gene amplification assessed by in situ hybridization (ISH) and protein overexpression assessed by immunohistochemistry (IHC) remain the primary predictors of responsiveness to HER2-targeted therapies in breast cancer. Data from NRG trial B-47 (ClinicalTrials.gov identifier: NCT01275677) released in late 2017 have now confirmed the lack of benefit from adjuvant trastuzumab for patients whose tumors lack gene amplification and are IHC 1+ or 2+, supporting current overall HER2 testing algorithms.5 Greater communication among health care providers (especially pathologists and oncologists) and appropriate infrastructure support for specimen handling and laboratory facilities have led to observed improvements in the analytic performance and accuracy of HER2 testing.6 The release of the 2007 HER2 testing guideline recommendations were associated with a meaningful reduction in the high frequency of false-positive HER2 test results,7 which allowed the 2013 Expert Panel to focus on providing additional guidance regarding less common HER2 testing scenarios.1,4 The HER2 Testing Expert Panel identified five clinical questions (listed in the Bottom Line box) that form the core of this 2018 Focused Update.7a,7b Clinical questions 1 and 2 were addressed in a previous correspondence by the Panel published in Journal of Clinical Oncology in 2015.8 Clinical questions 3, 4, and 5 address less common result groups observed when performing dual-probe ISH testing as described below.9,10 Since 2013, several laboratory and clinical investigators reported on the practical implications of the 2013 guideline update and the observed frequency of groups of less common HER2 test results, including ISH equivocal cases.9-13 With the new clinicopathologic data and availability of some limited clinical outcomes data on three less common HER2 dual-probe ISH test result groups, the Panel has revisited the most appropriate testing and interpretation algorithm and eliminated the ISH equivocal category. Most importantly, the Panel revised the diagnostic approach for three less common groups to include more-rigorous interpretation criteria for dual-probe ISH testing and to require concomitant IHC review to arrive at