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 (CTCs) and circulating tumor DNA (ctDNA) to predict prognosis in MBC. Experimental Design: We conducted a retrospective study of 91 patients with locally advanced and MBC. CTCs were enumerated by CellSearch; the plasma-based assay was performed utilizing Guardant360TM and the survival analysis using Kaplan-Meier curves. Results: 84 patients had stage IV cancer, 7 had no metastases. Eighty patients had CTCs analysis: median number 2 (0-5612). 232/277 (84%) blood samples had mutations. The average ctDNA fraction was 4.5% (0-88.2%) and number of alterations 3 (0-27); the most commonly mutated genes: TP53 (52%), PIK3CA (40%), ERBB2 (20%). At the time of analysis 36 patients (39.6%) were dead. The median follow-up for CTCs was 9 months; for ctDNA 9.9 months. For CTCs and ctDNA respectively, PFS was 4.2 and 5.2 months and 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); % ctDNA < 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's 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.

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