Aileen I Fernandez1, Matthew Liu1, Andrew Bellizzi2, Jane Brock3, Oluwole Fadare4, Krisztina Hanley5, Malini Harigopal1, Julie M Jorns6, M Gabriela Kuba7, Amy Ly8, Mirna Podoll9, Kimmie Rabe10, Mary Ann Sanders11, Kamaljeet Singh12, Olivia L Snir13, T Rinda Soong14, Shi Wei15, Hannah Wen7, Serena Wong1, Esther Yoon16, Lajos Pusztai17, Emily Reisenbichler1, David L Rimm1,17. 1. Department of Pathology, Yale University School of Medicine, New Haven, Connecticut. 2. Department of Pathology, The University of Iowa, Iowa City. 3. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. 4. Department of Pathology, University of California, San Diego. 5. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia. 6. Department of Pathology, Medical College of Wisconsin, Milwaukee. 7. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Department of Pathology, Massachusetts General Hospital, Boston. 9. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee. 10. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis. 11. Department of Pathology, Norton Healthcare, Louisville, Kentucky. 12. Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island. 13. Department of Pathology, Oregon Health & Science University, Portland. 14. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 15. Department of Pathology, University of Alabama at Birmingham. 16. Department of Pathology, MD Anderson Cancer Center, Houston, Texas. 17. Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut.
Abstract
IMPORTANCE: Trastuzumab deruxtecan (T-DXd) has shown efficacy in patients with breast cancer with ERBB2 immunohistochemistry (IHC) scores of 1+ or 2+ but not 0 as read in central pathology laboratories. The drug is currently being tested in large randomized clinical trials with registration intent for this patient population. OBJECTIVE: To determine the suitability of the current standard ERBB2 IHC assays to select patients with low ERBB2 positivity for treatment with T-DXd. DESIGN AND SETTING: Assessment of data from College of American Pathologists surveys and assessment of analytic data from a Yale University-based study of concordance of 18 pathologists reading 170 breast cancer biopsies. RESULTS: The total survey data set included scores over 2 years from 1391 to 1452 laboratories of 40 ERBB2 cores from each laboratory (20 cores twice a year for a total of 80). College of American Pathologists surveys show that 19% of cases read by the laboratories generate results with less than or equal to 70% concordance for IHC ERBB2 score 0 vs 1+. When 18 pathologists read the scanned slides from a selected set of breast cancer biopsies using a 4-point scale, there was only 26% concordance between 0 and 1+ compared with 58% concordance between 2+ and 3+. CONCLUSIONS AND RELEVANCE: In this study using a current standard ERBB2 IHC assay, the scoring accuracy for ERBB2 IHC in the low range (0 and 1+) was poor. This inaccuracy in the real world could lead to misassignment of many patients for treatment with T-DXd.
IMPORTANCE: Trastuzumab deruxtecan (T-DXd) has shown efficacy in patients with breast cancer with ERBB2 immunohistochemistry (IHC) scores of 1+ or 2+ but not 0 as read in central pathology laboratories. The drug is currently being tested in large randomized clinical trials with registration intent for this patient population. OBJECTIVE: To determine the suitability of the current standard ERBB2 IHC assays to select patients with low ERBB2 positivity for treatment with T-DXd. DESIGN AND SETTING: Assessment of data from College of American Pathologists surveys and assessment of analytic data from a Yale University-based study of concordance of 18 pathologists reading 170 breast cancer biopsies. RESULTS: The total survey data set included scores over 2 years from 1391 to 1452 laboratories of 40 ERBB2 cores from each laboratory (20 cores twice a year for a total of 80). College of American Pathologists surveys show that 19% of cases read by the laboratories generate results with less than or equal to 70% concordance for IHC ERBB2 score 0 vs 1+. When 18 pathologists read the scanned slides from a selected set of breast cancer biopsies using a 4-point scale, there was only 26% concordance between 0 and 1+ compared with 58% concordance between 2+ and 3+. CONCLUSIONS AND RELEVANCE: In this study using a current standard ERBB2 IHC assay, the scoring accuracy for ERBB2 IHC in the low range (0 and 1+) was poor. This inaccuracy in the real world could lead to misassignment of many patients for treatment with T-DXd.