HER-2 status of circulating tumor cells in a metastatic breast cancer cohort

Subtitle:a comparative study on characterization techniques

Background Personalized targeted treatment in metastatic breast cancer relies on accurate assessment of molecular aberrations, e.g. overexpression of Human Epidermal growth factor Receptor 2 (HER-2). Molecular interrogation of circulating tumor cells (CTCs) can provide an attractive alternative for real-time biomarker assessment. However, implementation of Cell-Search-based HER-2 analysis has been limited. Immunofluorescent (IF) image interpretation is crucial, as different HER-2 categories have been described. Major questions in CTC research are how these IF categories reflect gene expression and amplification, and if we should consider 'medium' HER-2 expressing CTCs for patient selection. Methods Tumor cells from spiked cell lines (n = 8) and CTCs (n = 116 samples) of 85 metastatic breast cancer patients were enriched using CellSearch. Comparative analysis of HER-2 expression by IF imaging (ACCEPT, DEPArray, and visual scoring) with qRT-PCR and HER-2/neu FISH was performed. Results Automated IF HER-2-profiling by DEPArray and ACCEPT delivered comparable results. There was a 98% agreement between 17 trained observers (visual scoring) and ACCEPT considering HER-2(neg) and HER-2(high) expressing CTCs. However, 89% of HER-2(med) expressing CTCs by ACCEPT were scored negative by observers. HER-2(high) expressing tumor cells demonstrated HER-2/neu gene amplification, whereas HER-2(neg) and HER-2(med) expressing tumor cells and CTCs by ACCEPT were copy-number neutral. All patients with HER-2-positive archival tumors had >= 1 HER-2(high) expressing CTCs, while 80% of HER-2-negative patients did not. High relative gene expression of HER-2 measured on enriched CTC lysates correlated with having >= 1 HER-2(high) expressing CTCs. Conclusion Automated images analysis has enormous potential for clinical implementation. HER-2 characterization and clinical trial design should be focused on HER-2(high) expressing CTCs.

Publication year:2019

Keywords:A1 Journal article

BOF-keylabel:yes

BOF-publication weight:2

CSS-citation score:1

Authors:International

Authors from:Higher Education

Accessibility:Open