A clinicopathological study of 30 breast cancer cases with a HER2/CEP17 ratio of ≥2.0 but an average HER2 copy number of <4.0 signals per cell

The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) have recently issued updated guidelines on human epidermal growth factor receptor 2 (HER2) testing by fluorescence in situ hybridization (FISH) in invasive breast cancers. Cases with a HER2/chromosome enumeration probe 17 (CEP17) ratio of ≥2.0 but an average HER2 copy number of <4.0 signals per cell (ISH group 2) are no longer automatically classified as ISH positive. Herein, 30 cases in ISH group 2 were collected. Another 100 patients with a HER2/CEP17 ratio <2.0 and <4.0 HER2 signals per cell (ISH group 5) and 100 patients with a HER2/CEP17 ratio of ≥2.0 and an average HER2 copy number of ≥4.0 signals per cell (ISH group 1) were also recruited for comparison. According to the 2018 ASCO/CAP guidelines, all the cases in ISH group 2 were categorized as HER2 negative. The clinicopathological characteristics of the patients in ISH group 2 were intermediate between ISH group 1 and group 5. Survival analyses revealed that there was no significant disease-free survival (DFS) and overall survival (OS) difference between patients with or without targeted therapy in ISH group 2, as well as between patients with targeted therapy in ISH group 1 and patients in ISH group 2. Patients without targeted therapy in ISH group 2 had a significantly worse OS than patients with targeted therapy in ISH group 1 and patients in ISH group 5. In conclusion, patients in ISH group 2 represent a biologically heterogeneous subset, which are different from those in ISH group 1 and 5. A larger cohort of patients in ISH group 2 should be included for future researches to define the efficacy of HER2-targeted therapy.