ASCO/CAP Clinical Practice Guideline Focused Update on HER2 Testing in Breast Cancer

As reported in the Journal of Clinical Oncology by Antonio C. Wolff, MD, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, and colleagues, ASCO and the College of American Pathologists (CAP) have issued a clinical practice guideline focused update on HER2 testing in breast cancer.  The focused update to the 2013 updated guideline was informed by expert panel review of published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns.

The panel was co-chaired by Dr. Wolff and M. Elizabeth Hale Hammond, MD, of Intermountain Healthcare and University of Utah School of Medicine.

Key Recommendations

  • Two recommendations addressed via correspondence with the Journal of Clinical Oncology 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 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.

Additional information is available at

The corresponding author for the Journal of Clinical Oncology article is ASCO.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.




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