Abstract P4-01-13: Clinical data in over 1,500 breast cancer patients across all stages of breast cancer with target selector circulating tumor cell technology
Authors: Fisher Deanna M , Huynh Lan , Sales Edgar V , Mayer Julie Ann , Singh Veena M 
Published: March 2020

Abstract
Clinical Data in Over 1,500 Patients Across All Stages of Breast Cancer with Target Selector Circulating Tumor Cell Technology Deanna M Fisher B.S., Lan Huynh B.S., Edgar V. Sales B.S., Julie Ann Mayer Ph.D., and Veena M. Singh M.D. Introduction: The detection and molecular characterization of circulating tumor cells (CTCs) in patients with breast cancer affords the ability to profile and monitor patients in real time for progression, risk stratification, recurrence, identification of potentially actionable therapeutic targets, and monitoring of treatment efficacy and emergence of resistance mechanisms. To harness the promise of CTC analysis a highly sensitive, robust, reproducible and clinically validated technology is required. Information acquired from a single tissue biopsy has temporal and spatial limitations; additionally, in patients with progressive/metastatic disease, a single biopsy may not be informative or in some instances difficult to perform and might fail to reflect inherent tumoral heterogeneity. CTCs on the other hand can provide a contemporaneous landscape of all cancerous lesions (primary and metastases) as well as the opportunity to track the evolving tumor genetic mechanisms. Methodology:Samples were collected in CEE Sure blood collection tubes and buffy coat isolation was performed using a percoll density gradient separation. Capture in the microchannel was performed after incubation with a ten-antibody capture cocktail followed by the addition of a biotinylated secondary antibody. The microchannels were stained with pan-cytokeratin cocktail, CD45, pan-CTC stain, DAPI and the following protein biomarkers (AR, ER, PR, and PDL1). Following enumeration of the CTCs, the microchannels were subsequently sent for multi-color FISH biomarkers such as HER2. Results: 1,687 patients across all stages of breast cancer and treatment time points (pre- treatment, post-treatment, on treatment) were analyzed. CTCs were detected up to 70% of the time across early to late stage patients. The dynamic range of CTC detection and enumeration in a single microfluidic channel (8mL blood) ranged from 1 to 38,419 CTCs. CTC detection has been previously validated to a 1 CTC limit of detection. CTCs identified varied in both size and antigen profile. Target Selector CTC platform technology identifies both cytokeratin positive and cytokeratin negative phenotypes of CTCs. Biomarker interrogation was undertaken in all CTC subtypes by FISH probes (Fluorescent in situ hybridization) and ICC (Immunocytochemical) antibody clones similar to those used on tissue sections. Genomic alterations commonly detected in breast cancer (i.e. HER2 amplification, ER) were detected in all CTC subtypes. HER2 amplification was identified in 15% of cases with CTCs detected and ER in 24 %. Conclusions: This data demonstrates the ability of the Target Selector CTC Platform to accurately detect, enumerate, and interrogate for genomic alteration across a broad spectrum of CTC phenotypes spanning various clinical and treatment stages. This enables clinicians and patients a more real time option to profile and monitor disease. The Target Selector CTC technology allows for the analysis of a broader spectrum of CTC phenotypes thus increasing the likelihood of identifying actionable biomarkers for risk stratification, recurrence, potential treatment selection and monitoring for emergence of resistance.
Citation Format: Deanna M Fisher, Lan Huynh, Edgar V Sales, Julie Ann Mayer, Veena M Singh. Clinical data in over 1,500 breast cancer patients across all stages of breast cancer with target selector circulating tumor cell technology [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-13.