The American Society of Clinical Oncology/College of American Pathologists updated the human epidermal growth factor receptor 2 (HER2) breast carcinoma testing guideline in 2018 to address issues from uncommon HER2 fluorescence in situ hybridization (FISH) results. Based on the 2013 American Society of Clinical Oncology/College of American Pathologists guideline, cases wherein the HER2/chromosome 17 centromere (CEP17) ratio of 2.0 or more with an average HER2 copy number of less than 4.0 were considered in situ hybridization (ISH) positive. Under the 2018 guideline, such cases are classified as ISH Group 2 and are no longer considered eligible for anti-HER2 therapy when the corresponding HER2 immunohistochemistry result is 0, 1+, or 2+.


To assess the clinical, pathologic, and treatment aspects of patients with ISH Group 2 results.


We retrospectively reviewed HER2 FISH results at our center between January 2012 and December 2014 and identified and characterized cases with ISH Group 2 results.


Thirty-nine cases with ISH Group 2 results from 39 patients were reviewed. Twenty of 39 (51%) patients received anti-HER2 therapy. Patients treated with HER2-targeted therapy were less likely to have hormone receptor–positive tumors, compared with patients without anti-HER2 treatment, though not significantly (P = .30). The only significant difference between the 2 patient groups was receipt of cytotoxic chemotherapy treatment (P < .001). Overall, clinical outcome was similar between the 2 groups (P > .99).


This retrospective study with median follow-up of at least 6 years shows patients with ISH Group 2 tumors had similar clinical outcomes, irrespective of HER2-targeted therapy. Further analysis in the prospective setting would provide valuable data that would potentially inform clinical decision making.

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Author notes

The authors have no relevant financial interest in the products or companies described in this article.

The abstract for this paper was presented virtually at the 110th annual meeting of the United States and Canadian Academy of Pathology on March 17, 2021.