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Breast cancer (BC) affects 1 in every 8 women in the United States and is currently the most prevalent cancer worldwide. Precise staging at diagnosis and prognosis are essential components for the clinical management of BC patients. The liquid biopsy (LBx) has promising applications in cancer screening and early diagnosis ultimately leading to better survival results and less disease burden. In this study, we evaluated the feasibility of the high-definition single cell assay (HDSCA) LBx platform to stratify disease states (early- and late-stage BC) and normal donors using peripheral blood samples. In the HDSCA3.0 workflow, both common white blood cells (WBCs) and rare cells, including circulating tumor cells (CTCs), EMT and platelet-coated cells, plus acellular structures are identified and classified computationally from scanned immunofluorescent images. This comprehensive LBx approach provides a quantitative landscape view of each individual case. In a striking example of the insight provided by HDSCA, we compared LBx results for early-stage and late-stage BC patients with two independent cohorts of normal donors to show the utility of a blood draw as a source of biomarkers for early-stage cancer detection. As expected, CTCs were detected at a higher level in late-stage patients, compared to either the early-stage or normal donors. Surprisingly, however, we observed a significantly higher incidence of tumor-associated large extracellular vesicles (LEVs) in the early-stage patients, compared to the other two groups. A patient-level classification model was able to correctly classifying LBx profiles as normal, early, or late with LEV enumeration as the strongest predictor, followed by epi.CTC enumeration. We will present a reproducible LBx profile of rare cells and LEVs of early-stage disease compared to late-stage BC and normal donors with high accuracy, allowing for robust stratification. Our findings illustrate the feasibility of the LBx to assess early disease states prior to clinically defined metastasis, stratified from normal donors, highlighting the general consideration of the liquid biopsy for the diagnostic work-up and potentially screening. Citation Format: Stephanie Shishido, Peter Kuhn, Jeremy Mason, James Hicks, Rafael Nevarez, Nicholas Matsumoto, Anand Kolatkar, Carmen Ruiz Velasco, Amanda Anderson, Michael Kidd, Kathy Wilkinson, E Shelley Hwang, Janice Lu, Jorge Nieva, Nikki Higa, Amin Naghdloo, Olivia Hart, Sonia Maryam Setayesh. Multianalyte liquid biopsy to aid the diagnostic workup of breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-05-09. |
