Identification of HER2 Immunohistochemistry-Negative, FISH-Amplified Breast Cancers and Their Response to Anti-HER2 Neoadjuvant Chemotherapy.

Objectives: Either immunohistochemistry (IHC) or in situ hybridization (ISH) can be used to determine human epidermal growth factor receptor 2 (HER2) status. Breast cancers (BCs) with HER2 IHC-negative (IHC-) and ISH-amplified (ISH+) results have been rarely reported but not well studied. We investigated the frequency of HER2 IHC-/ISH+ BCs and their response to anti-HER2 neoadjuvant chemotherapy (NAC).
Methods: Seventeen BCs with HER2 IHC-/ISH+ results were identified from 1,107 consecutive invasive BCs (1.5%, 17/1,107).
Results: Gene protein assay confirmed the original HER2 IHC and ISH results. Increased HER2 RNA level was detected in HER2 IHC-/ISH+ cases compared with HER2 IHC-/ISH- cases. Eight patients had anti-HER2 NAC; three had pathologic complete response, and five had residual tumors. Conclusions: A small percentage of patients (1.5%) showed discordant HER2 IHC and ISH results (IHC-/ISH+) and would have lost the opportunity for potentially beneficial anti-HER2-targeted therapy if only HER2 IHC testing had been used.