Abstract P4-01-07: A comprehensive liquid biopsy in patients undergoing neoadjuvant therapy

Background: Precision medicine is revolutionizing breast cancer (BC) care. Comprehensive liquid biopsies are a tool for personalized care in patients with locally advanced breast cancer (LABC). Identifying robust biomarkers as part of a comprehensive liquid biopsy to predict response to treatment is of immense clinical interest. Methods: After obtaining IRB approval, serial blood samples were collected from patients with LABC undergoing neoadjuvant therapy. Paired biopsies were collected prior to treatment and were sent to Foundation Medicine for next-generation sequencing (NGS). We used a sized-base microfilter technology to capture circulating tumor cells (CTCs) and circulating cancer associated fibroblasts (cCAFs). Patients with one or more CTCs or cCAFs were deemed positive for these tests. Additionally, in collaboration with Foundation Medicine, we extracted circulating tumor DNA (ctDNA) and we analyzed it using the FoundationACT platform. Patients with a detectable genomic alteration in their plasma were considered as having a positive ctDNA test. Our primary objective is to determine if a comprehensive liquid biopsy can serve as a prognostic marker of pathologic complete response (pCR). Results: For this analysis we describe our findings in the initial blood draw of the first 18 patients enrolled. The mean age is 54 years (38-70). All patients who had their tumors sequenced had a detectable mutation. Consistent with the findings of others, we found TP53 mutations to be the most prevalent at 83.3%. We found that 44% of patients had ctDNA, 68.4% had cCAFs and 78.9% had CTCs. Many patients also had clusters of cells, consisting of one cell type, or co-clusters, consisting of both. 38.9% had CTC clusters, 16.7% had cCAF clusters and 16.7% had co-clusters (CTCs and cCAFs together). Some patients with CTCs did not have cCAFs and vice versa. The number of CTCs and cCAFS did not correlate with stage of disease or receptor status. Conclusions: We describe a comprehensive liquid biopsy combining a sized-based microfilter technology for CTC and cCAFs identification and the FoundationACT platform for ctDNA analysis is feasible and these biomarkers can be detected in patients with LABC prior to the initiation of neoadjuvant therapy. Our study is accruing rapidly, and we will update our results with the longitudinal collection and the prognostic value of a comprehensive liquid biopsy at the time of the meeting. Citation Format: Sandoval Leon AC, Medina Saenz K, Miller P, Benson A, Calfa C, Mahtani R, Slingerland J, Perez A, Vogel C, Valdes-Albini F, El-Ashry D, Lippman M. A comprehensive liquid biopsy in patients undergoing neoadjuvant therapy [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 P4-01-07.