Molecular Pathway and Fluorescence In Situ Hybridization Testing of ERBB2 (HER2) Gene Amplification in Invasive Ductal Carcinoma of Breast

  • Tomasz Jodlowski
  • K. H. RameshEmail author


Standard screening of breast tumors involves morphologic, immunohistochemistry (IHC), and Fluorescence in Situ Hybridization (FISH) analyses to assess pathogenicity and to identify possible treatment strategies. Among breast cancer types, invasive ductal carcinoma (IDC), in particular, exhibits amplification of the HER2 (ERBB2) gene that can be detected by FISH as defined by the current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP, 2013, 2018) scoring guidelines. One criterion for amplification of the HER2 gene is based on the ratio of HER2 gene signals to centromere 17 signals obtained from microscopic analysis of 20 cells by FISH. A second criterion requires an average of more than 6 copies of HER2 signals per cell out of 20 cells screened by FISH. If either of these criteria is met, then individualized therapy with adjuvant chemotherapy and the HER2-targeted drug Trastuzumab (Herceptin®) is indicated, which remarkably improves prognosis by decreasing local recurrence and metastasis. If HER2 is not amplified in IDC of breast, further testing is performed and alternative treatments are considered which may have less favorable prognoses. Genetic heterogeneity (GH) is when IDC of breast has between 5 and 50% of cells that are positive for HER2 amplification by FISH. Such cases fall short in meeting the amplified status criteria currently mandated by ASCO/CAP. Based on our, and data from literature review, an update to the most recent ASCO/CAP guideline (issued in June 2018) criteria for positive amplification to include HER2 GH+ cases with greater than 25% HER2 amplification would extend the beneficial HER2-targeted therapy that is regulated by ASCO and the FDA to an additional 8% of patients .


HER2 ERBB2 FISH Immunohistochemistry IHC Breast cancer ASCO/CAP Genetic heterogeneity Amplification Invasive ductal carcinoma Ductal carcinoma in situ Trastuzumab Herceptin ERBB2 update 


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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of PathologyMontefiore Medical Center and Albert Einstein College of MedicineBronxUSA
  2. 2.Clinical Cytogenetics and Genomics, Department of PathologyMontefiore Medical Center and Albert Einstein College of MedicineBronxUSA

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