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J Clin Oncol. 2018 Jul 10;36(20):2105-2122. doi: 10.1200/JCO.2018.77.8738. Epub 2018 May 30.

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

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Antonio C. Wolff, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore; Lisa M. McShane, National Cancer Institute, Bethesda, MD; M. Elizabeth Hale Hammond, Intermountain Healthcare and University of Utah School of Medicine, Salt Lake City, UT; Kimberly H. Allison, Stanford University School of Medicine, Stanford; Patrick Fitzgibbons, St Jude Medical Center, Fullerton; Michael F. Press, University of Southern California, Los Angeles, CA; Brittany E. Harvey and Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA; John M.S. Bartlett, Ontario Institute for Cancer Research; Wedad Hanna, Sunnybrook Health Sciences Centre and Women's College Hospital, Toronto, Ontario, Canada; Michael Bilous, Western Sydney University and Australian Clinical Laboratories, Sydney, New South Wales, Australia; Ian O. Ellis, The University of Nottingham, Nottingham; Mitchell Dowsett, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Robert B. Jenkins, Mayo Clinic, Rochester, MN; Patricia A. Spears, Cancer Information and Support Network, Raleigh, NC; Gail H. Vance, Indiana University School of Medicine, Indianapolis, IN; and Giuseppe Viale, University of Milan and Istituto Europeo di Oncologia, Milan, Italy.


Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at .


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