HER2: Closing the Gap Between Laboratory Testing and Clinical Practice

Abstract

Laboratory testing for human epidermal growth factor receptor 2 (HER2) status is critically important for the management of care of patients with breast cancer, especially for therapeutic decision making.1 Although the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines reaffirmed the importance of quality assurance in diagnostic testing for the HER2 gene and its protein product,2 a recent UK National External Quality Assurance Scheme (NEQAS) on HER2 testing by in situ hybridization showed modest performance, in that the percentage of laboratories achieving “appropriate” results ranged from 45% to 88%, whereas the percentage achieving “inappropriate” results ranged from 5% to 29%.3 Recent technological developments have created a new generation of laboratory diagnostics, sometimes identified with the term “omics,” which holds promise for better means of detecting diseases and monitoring response to treatment. However, as regards laboratory testing, there is evidence that not only recent research findings but also “old” research outcomes have simply been “lost in translation.”4 This, in turn, stresses the need for a more effective process to carry on translational research, involving also laboratory professionals. Recently, the need was emphasized for establishing an international collaboration to set standards and methods to evaluate laboratory diagnostic tests, primarily in terms of analytic performance, but also considering their clinical validity, clinical usefulness, and, finally, ethical and social implications. The story of HER2 testing well illustrates the evidence gap between diagnostic testing and clinical practice, unveiling the problems of reliability, accuracy, and standardization of diagnostic tests. More intriguingly, however, it highlights the need for correct interpretation and use of laboratory information, which are still areas of major improvement in diagnostics. An interesting lesson we have recently learned from HER2 testing is that only invasive testing, immunohistochemical analysis or fluorescence in situ hybridization (FISH), on human tissues has …