Cell-Free DNA and Circulating Tumor Cells: Comprehensive Liquid Biopsy Analysis in Advanced Breast Cancer.

Abstract

<b>Purpose:</b> Liquid biopsy provides a real-time assessment of metastatic breast cancer (MBC). We evaluated the utility of combining circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) to predict prognosis in MBC.<b>Experimental Design:</b> We conducted a retrospective study of 91 patients with locally advanced breast cancer and MBC. CTCs were enumerated by CellSearch; the plasma-based assay was performed utilizing Guardant360 and the survival analysis using Kaplan-Meier curves.<b>Results:</b> Eighty-four patients had stage IV cancer, and 7 patients had no metastases. Eighty patients had CTC analysis: median number 2 (0-5,612). Blood samples [232 of 277 (84%)] had mutations. The average ctDNA fraction was 4.5% (0-88.2%) and number of alterations 3 (0-27); the most commonly mutated genes were <i>TP53</i> (52%), <i>PIK3CA</i> (40%), and <i>ERBB2</i> (20%). At the time of analysis, 36 patients (39.6%) were dead. The median follow-up for CTCs was 9 months; for ctDNA, it was 9.9 months. For CTCs and ctDNA, respectively, progression-free survival (PFS) was 4.2 and 5.2 months and overall survival (OS) was 18.7 and 21.5 months. There was a statistically significant difference in PFS and OS for baseline CTCs < 5 versus CTCs ≥ 5 (<i>P</i> = 0.021 and <i>P</i> = 0.0004, respectively); %ctDNA < 0.5 versus ≥ 0.5 (<i>P</i> = 0.003 and <i>P</i> = 0.012); number of alterations < 2 versus ≥ 2 (<i>P</i> = 0.059 borderline and <i>P</i> = 0.0015). A significant association by Fisher exact test was found between the number of alterations and the %ctDNA in the baseline sample (<i>P</i> < 0.0001).<b>Conclusions:</b> The study demonstrated that liquid biopsy is an effective prognostic tool. <i>Clin Cancer Res; 24(3); 560-8. ©2017 AACR</i>.