Abstract P3-10-12: ERBB2 copy number analysis of invasive breast carcinoma using digital droplet PCR and targeted next-generation sequencing: A focus on 'non-classical' HER2 FISH groups using the 2018 ASCO/CAP HER2 testing guideline

Background: Non-classical HER2 FISH results were recently reclassified in the 2018 HER2 guidelines update, and concurrent IHC testing was recommended as part of additional workup to determine the final HER2 status in these groups. In this study, we explored the genomic landscape of HER2 FISH groups using digital droplet PCR (ddPCR) and targeted next-generation sequencing (NGS) on invasive breast carcinomas. Methods: Fifty-one clinical samples with HER2 FISH and IHC results were included in our analysis and classified into FISH groups based on the updated 2018 ASCO/CAP HER2 testing guideline: (i) Group 1A with ratio ≥2 and signals/cell ≥6, (ii) Group 1B with ratio ≥2 and signals/cell ≥4 and 50% of exons). Results: Mean ddPCR ratios varied amongst the different FISH groups (P Conclusion: ERBB2 amplification using ddPCR and NGS is correlated with HER2 overexpression in both classical and non-classical FISH groups, thus providing genomic evidence to support the recent recommendation for concurrent IHC testing in cases with unusual FISH results. Our findings also highlight a potential role of ddPCR and targeted NGS in the workup of challenging HER2 cases. Citation Format: Yang S-R, Bouhlal Y, De La Vega FM, Ballard M, West RB, Sibley RK, Kuo CJ, Vilborg A, Allison KH. ERBB2 copy number analysis of invasive breast carcinoma using digital droplet PCR and targeted next-generation sequencing: A focus on 9non-classical9 HER2 FISH groups using the 2018 ASCO/CAP HER2 testing guideline [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-12.