Abstract A044: Utilizing breast cancer-specific micronuclei DNA features from erythrocytes for early detection of breast carcinoma

Abstract Background: Alongside traditional imaging, current development in non-invasive breast carcinoma (BC) diagnosis, such as cell-free DNA-based technologies, have demonstrated promising potential in BC diagnosis. However, achieving early detection remains a challenge. Micronuclei (MN) are extranuclear bodies containing damaged chromosome segments indicative of genomic instability. Elevated levels of MN-containing erythrocytes have been studied in genotoxicity testing and cancer diagnosis. Here, we sequenced the isolated and purified micronuclei DNA (MN-DNA) from erythrocytes in 2ml peripheral blood using a method we previously developed (WO2021/228246 A1) and identified a series of distinct features in read counts that enabled to detect early-stage BC patients. Methods: We collected a clinical study cohort of 172 BC patients and 216 non-BC controls from 1-2ml peripheral blood. MN-DNA was isolated from erythrocytes and performed whole-genome sequencing. We selected distinctive tumor-associated MN-DNA features identified by genome-wide analysis to differentiate between controls and BC for KEGG pathway enrichment and constructed a classification model based on these features. Results: Genome-wide analysis of MN-DNA revealed significant regions between controls and BC patients. Based on covered genes, we observed significant enrichment in the estrogen signaling pathway. Utilizing these distinct MN- DNA features, we constructed a classification model that achieved an AUC of 96%, with a 95% specificity and 88% sensitivity in the test cohort. The model identified early BC (stage 0-I) and advanced BC (stage II-IV) with sensitivities of 100% or 84%, respectively. Conclusions: Our findings highlight that MN-DNA, a form of cytoplasmic DNA, provides a valuable tool for the accurate detection of BC, particularly in its early stages. The MN-DNA pattern is linked to the estrogen signaling pathway, offering novel insights and mechanisms that differ from current diagnostic approaches. Research sponsor: Timing Biotech. Early Detection of Primary Cancer and Relapse Citation Format: Wenjv Mo, Xingyun Yao, Haobo Sun, Honghao Liang, Jie Jin, Xiaowen Ding, Xiaofei Gao. Utilizing breast cancer-specific micronuclei DNA features from erythrocytes for early detection of breast carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A044.