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

Purpose: 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. Experimental Design: 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. Results: 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 alpha DNA fraction was 4.5% (0-88.2%) and number of alterations 3 (0-27); the most commonly mutated genes were TP53 (52%), PIK3CA (40%), and ERBB2 (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 (P = 0.021 and P = 0.0004, respectively); %alpha DNA < 0.5 versus >= 0.5 (P = 0.003 and P = 0.012); number of alterations < 2 versus >= 2 (P = 0.059 borderline and P = 0.0015). A significant association by Fisher exact test was found between the number of alterations and the % ctDNA in the baseline sample (P < 0.0001). Conclusions: The study demonstrated that liquid biopsy is an effective prognostic tool. (C) 2017 AACR.