Abstract PS5-01-01: Concordance of genomic alterations between paired tissue (T) and plasma (P) samples analyzed with next generation sequencing (NGS) panels from patients (pts) with HER2-positive metastatic breast cancer (mBC)

Abstract BACKGROUND: Analyses of P circulating tumor DNA by NGS panels is an emerging useful tool for identifying tumor genomic alterations in BC. There is scarce data about the concordance of genomic alterations found at the same time point in T and P samples of pts with HER2-positive mBC. MATERIALS AND METHODS: This is a single institution study of a consecutive cohort of HER2-positive mBC pts receiving anti-HER2 therapies. Tumor T and P samples were collected prospectively after obtaining consent. Genomic alterations were analyzed retrospectively using NGS with the VHIO300 panel for T (includes 421 genes) and the VHIO360 panel for P samples (includes 74 genes). HER2 expression in T samples was evaluated using Immunohistochemistry (IHC) and in situ hybridization (ISH) following the 2013 ASCO/CAP guidelines. To test the concordance of paired T/P samples between the NGS panels, only the 73 common genes were included. General linear models, Pearson and Spearman correlations were used to associate numerical variables. Results: 107 consecutive pts were included in the study, of which 39 pts had synchronous paired T/P samples. Out of these 39 pts, a total of 42 T/P pairs were available. T samples were analyzed with VHIO300 panel and IHC/ISH, while P samples were tested with VHIO360. Concordance in the presence or absence of ERBB2 amplification status between P and T was coincident in 30 out of 42 pairs (71%) showing a statistically significant correlation with copy number. As a reference, in T samples alone, the concordance between ERBB2 amplification detected by two different methodologies, NGS and by IHC/ISH, resulted positive in 35 out of 42 samples (83%). T and P shared at least one pathogenic or likely pathogenic mutation in 32 out of 42 pairs (76%) where these variants were present. The overall agreement between genotype status (mutant/ wild-type) for all genes was 78.5%. The number of detected mutations per sample varied from 0 - 6. For variants of uncertain significance (VUS), 8 of 38 pairs (21%) shared altered variants in both samples. The average percentage of altered shared genes was 35%. The range of VUS variants detected per sample varied from 0 - 14. For amplifications 26 pairs (65%) out of 40 shared at least one altered gene in both samples. The average percentage of concordant T/P pairs with regards to amplified genes was 60.8%. The range of copies detected per sample varied from 0 - 9. Concordance of genomic alterations found in paired T/P samples is summarized in the table. Conclusions: A high concordance rate for ERBB2 amplification was detected by NGS in T and P paired samples, as well as in T samples using different approaches, NGS and IHC/ISH. Concordance was high between T and P with regards to pathogenic and likely pathogenic mutations, moderate for amplifications other than ERBB2, and overall low for VUS. Citation Format: S. Escrivá-de-Romaní, L. Ollé-Monràs, L. Joval-Ramentol, E. Álvarez Colomé, M. Arumí, A. Rezqallah, A. Suñol, J. Jimenez, E. Castillo, R. Fasani, P. Martinez, A. Baizán, M. Oliveira, M. Bellet, E. Zamora, I. Pimentel, M. Borrell, N. Gómez, A. Rodríguez, M. Perachino, V. Barberi, M. Gaudio, C. Salvà de Torres, E. Cimbro, R. Dienstmann, J. Seoane, P. Nuciforo, A. Vivancos, C. Saura. Concordance of genomic alterations between paired tissue (T) and plasma (P) samples analyzed with next generation sequencing (NGS) panels from patients (pts) with HER2-positive metastatic breast cancer (mBC) abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-01-01.