Longitudinal Dynamics of Circulating Tumor Cells and Circulating Tumor DNA for Treatment Monitoring in Metastatic Breast Cancer.

Liquid biopsy-based biomarkers, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are increasingly important for the characterization of metastatic breast cancer (MBC). The aim of the study was to explore CTCs and ctDNA dynamics to better understand their potentially complementary role in describing MBC. METHODS: The study retrospectively analyzed 107 patients with MBC characterized with paired CTCs and ctDNA assessments and a second prospective cohort, which enrolled 48 patients with MBC. CTCs were immunomagnetically isolated and ctDNA was quantified and then characterized through next-generation sequencing in the retrospective cohort and droplet digital polymerase chain reaction in the prospective cohort. Matched pairs variations at baseline, at evaluation one (EV1), and at progression were tested through the Wilcoxon test. The prognostic role of ctDNA parameters was also investigated. RESULTS: Mutant allele frequency (MAF) had a significant decrease between baseline and EV1 and a significant increase between EV1 and progression. Number of detected alterations steadily increased across timepoints, CTCs enumeration (nCTCs) significantly increased only between EV1 and progression. MAF dynamics across the main altered genes was then investigated. Plasma DNA yield did not vary across timepoints both in the retrospective cohort and in the prospective cohort, while the short fragments fraction showed a potential role as a prognostic biomarker. CONCLUSION: nCTCs and ctDNA provide complementary information about prognosis and treatment benefit. Although nCTCs appeared to assess tumor biology rather than tumor burden, MAF may be a promising biomarker for the dynamic assessment of treatment response and resistance.

Performance of a novel Next Generation Sequencing circulating tumor DNA (ctDNA) platform for the evaluation of samples from patients with metastatic breast cancer (MBC).

Circulating tumor DNA (ctDNA) is gaining momentum as sensitive diagnostic tool for advanced disease characterization because of its ability both to capture the tumor's heterogeneity and its dynamic adaptations. However, the consistency between all the available platforms is still debated. The aim of the study was to explore the performance of the novel diagnostic NGS platform PredicinePLUS™ and to compare its results with the clinically available Guardant360™ platform for possible analytical inconsistencies. The study suggests that PredicinePLUS™ NGS platform can detect genomic alterations and measure allele frequency in samples of MBC patients and confirmed that different NGS platforms could be potentially compared provided that certain sample management and analytical requirements are met.