Background: Circulating tumor DNA (ctDNA) have been increasingly used as a minimal invasive test to detect genomic alterations of cancer patients.

Methods: We performed a retrospective analysis of blood samples from mBC patients (pts) collected at baseline, on-treatment, and disease progression. A highly sensitive, plasma-derived ctDNA-based NGS assay (PredicinePLUS, a comprehensive 180 key cancer gene panel) was used to detect somatic mutations and copy number variations in ctDNA with an in-house propriety algorithm.

Results: In this study, we evaluated 162 blood samples from 109 mBC pts who underwent systematic therapy at Beijing Cancer Hospital with approval from Research Ethics Committee. 129 samples from 92 pts passed NGS quality check, and were included in the analysis. Among these pts, the percent of HR+, HER2+ and Triple-Negative pts is 36.8%, 29.5% and 31.5%, respectively. About 86% samples contain somatic mutations and/or copy number variations. Collectively, 372 somatic mutations (SNV and Indels) were detected on 76 genes, among which TP53 (44.2%), PIK3CA (25.3%), BRCA2(10.5%) and ATM (10.5%) were frequently altered with frequency varying across different subtypes. ESR1 hotspot mutations ((D538G and Y537S/N/C) were also detected in a subset of HR+ patients. Copy number gain or loss was detected on 32 genes, including amplification of ERBB2, PIK3CA, FGFR1 and deletion of CDKN2A, ATM, RB1 etc. Importantly, ERBB2 copy number amplifications were only detected in HER2 IHC positive cases for base-line samples, leading to 68% sensitivity and 100% specificity. Interestingly, ctDNA yield increased as disease progressed, suggesting ctDNA yield may serve as a potential biomarker for predicting treatment response and monitoring disease progression. Additional genomic alterations that change dynamically along with the course of treatment or associate with drug response and/or resistance were also identified.

Conclusions: This study demonstrated ctDNA-based genomic analysis was highly sensitive and specific in detecting various genomic alterations, consistent with other published studies. It also suggests that HER2 copy number amplification could be robustly assessed in a non-invasive manner.

Citation Format: Yu J, Li H, Zhang S, Wang A, Zhao Z, Liu X-R. Molecular characterization of circulating tumor DNA in Chinese metastatic breast cancer (mBC) patients [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 P4-01-13.