Abstract IA004: Early cancer dissemination: Circulating tumor cells in ductal carcinoma in situ patients

Abstract Raised awareness about the importance of early breast cancer diagnostics has led to an increased detection rate of ductal carcinoma in situ (DCIS) through mammographic screening. DCIS, often termed as 'Stage 0' carcinoma, is characterized by neoplastic cells confined within the basement membrane. Despite the significant treatment efforts for most DCIS patients, the 20-year breast cancer mortality rate post-diagnosis, with or without treatment, remains at 3.3%. To deepen the understanding of breast cancer oncogenesis, recent studies have highlighted the clonal diversity within the DCIS tumor microenvironment and the presence of disseminated tumor cells in DCIS patients. Nonetheless, significant gaps persist in identifying diagnostic characteristics that predict which DCIS patients are more likely to experience progression or recurrence. Ultimately, this project aims to enhance DCIS patient stratification through the high-throughput isolation and analysis of circulating biomarkers. In this study, we establish a novel workflow that addresses the limitations of traditional tissue-based diagnostics by transitioning to liquid biopsies. This research not only builds upon emerging evidence of early breast cancer cell dissemination during carcinogenesis but also explores the utility of circulating tumor cells (CTCs) as biomarkers in DCIS. The use of the labyrinth, a high-throughput inertial microfluidic device, has shown success in isolating CTCs based on their larger size relative to white blood cells. Unlike antigen- based isolation methods, inertial microfluidic devices can capture heterogeneous CTCs with varying surface proteins. Leveraging this technology, we successfully isolated and identified CTCs in DCIS patients. Furthermore, single-cell RNA sequencing of the isolated DCIS CTCs allowed us to identify prognostically significant signatures. Overall, our study presents a workflow capable of identifying characteristics associated with a greater risk of progression, thus contributing valuable insights into the stratification and management of DCIS patients. Citation Format: Sunitha Nagrath, Neha Nagpal, Brittany Rupp, Yan Hong, Fariba Behbod, Max Wicha. Early cancer dissemination: Circulating tumor cells in ductal carcinoma in situ patients [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 IA004.