Abstract PS2-25: Cell-free DNA based detection of mono-allelic versus bi-allelic loss of function for essential genes in breast cancer

Abstract

Abstract Background: Breast cancer is the top cancer in women, accounting for over 30% of new cancer cases in women worldwide. Breast cancer is a highly heterogenous disease. Treatment of breast cancer is a very active area in cancer research with significant progresses in recent years. Despite of recent progress in liquid biopsy molecular profiling, blood-based detection of mono-allelic versus bi-allelic loss of function for essential genes such as BRCA, PTEN etc. remains an unmet clinical need for targeted therapy in breast cancer. Methods: We tested over 1000 plasma samples of breast cancer patients using PredicneCARE, a proprietary cell-free DNA (cfDNA) assay, which covered the DNA Damage Repair (DDR) genes in addition to most genes under research in cancer pathways. This blood-based cfDNA assay has a well-tuned capability to reliably detect copy number gain and loss, discriminating bi-allelic versus mono-allelic gene deletions. The assay also has an HRD (Homologous Recombination Deficiency) add-on for the generation of HRD score. Results: PredicineCARE was used to test over 1000 breast cancer patients. The most frequently mutated genes include TP53(59.7%), PIK3CA(47.6%), BRCA2(16.1%), ATM(12.9%), ESR1(12.1%), and ARID1A(10.1%), with cancer variant detection capability down to 0.1% for hotspots; for copy number gain at ≥2.23 and for copy number loss at ≤1.75; and for rearrangements at 0.375%. Interestingly, cfDNA-based gene amplifications were founded in ERBB2, PIK3CA, FGFR1, MYC, etc. and gene deletions were found in important genes such as PTEN, RB, BRCA1/2 etc. Interestingly, we observed significant difference in mutations of key driver genes such as PIK3CA in Chinese versus Caucasian mBC cohorts. Conclusion: The PredicineCARE assay detects blood-based cancer alterations including copy number loss, fusion detection and somatic status evaluation, providing a non-invasive approach to profile important targets including HER2, EGFR, VEGFR, DNA damage repair (BRCA1/2), cell cycle and growth regulations (CDK4/6-RB and PTEN/PI3K/AKT/mTOR), and TRK/ROS1/RET fusions for the treatment of breast cancer. Citation Format: Feng Xie, Haoran Tang, Yue Zhang, Yong Huang. Cell-free DNA based detection of mono-allelic versus bi-allelic loss of function for essential genes in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-25.