Should a borderline negative HER2 result in a core biopsy of invasive carcinoma of the breast have HER2 assessment repeated in the excision specimen?

• Published in: Journal of clinical pathology Vol. 77; no. 11; p. 726
• Main Authors: Lee, Andrew H S, Hodi, Zsolt, Abbas, Areeg, Wencyk, Peter, Ellis, Ian O, Rakha, Emad
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 20.10.2024
• Subjects: Adult; Aged; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biopsy; Biopsy, Large-Core Needle; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Chemotherapy; Chromosomes; Female; Gene Amplification; Humans; Immunohistochemistry; In Situ Hybridization; In Situ Hybridization, Fluorescence; Laboratories; Middle Aged; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Tumors; United Kingdom > UK; carcinoma; breast; in situ hybridisation
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp-2023-209091

The 2015 UK guidelines for HER2 assessment in breast cancer recommended repeat assessment if the core biopsy was scored as 2+ on HER2 immunohistochemistry (IHC) with borderline negative in situ hybridisation (ratio of number of HER2 to chromosome 17 centromere copies of 1.8-1.99). This case series aimed to assess the value of such repeat assessment in the surgical specimen, in particular the proportion that were HER2 positive. Details of biopsies with 2+ IHC and borderline negative in situ hybridisation were extracted from a database. The results of repeat HER2 testing in the surgical specimen for this cohort study were then obtained. 112 patients with no preoperative treatment had repeat assessment: 4 were 3+ and 16 were 2+ amplified. Of 14 with preoperative chemotherapy, 1 was 3+ and 4 were 2+ amplified. All the 2+ amplified carcinomas had a HER2 to chromosome 17 ratio less than 4, in 50% the ratio was between 2.0 and 2.2, and in 50% the HER2 copy number was less than 4. Repeat assessment yielded 4% 3+ results and 14% 2+ amplified carcinomas but with low level amplification. These results suggest that retesting of borderline negative HER2 cases should be optional and no longer mandatory.