The aim of this study was to assess the prognostic and predictive value of an untargeted assessment of tumor fractions in the plasma of metastatic breast cancer patients and to compare circulating tumor DNA (ctDNA) with circulating tumor cells (CTC) and conventional tumor markers.
Patients and methods: 29 patients with metastatic breast cancer were included in this single-institution observational cohort study. Blood samples were obtained at first diagnosis of metastases, during several lines of treatment, and/or at every further moment of progression/development of new metastases. We assessed tumor fractions in plasma using an untargeted mFAST-SeqS method. CTCs were captured using a sized-based microfilter and identified as nucleated, cytokeratin positive/CD45 negative cells. Resulting ctDNA z-scores were compared to tumor fractions established with the recently published ichorCNA algorithm and associated with the clinical outcome.
We observed a close correlation between mFAST-SeqS z-scores and ichorCNA ctDNA quantifications. Patients with mFAST-SeqS z-scores above three (34.5%) showed significantly worse overall (p = 0.014) and progression-free survival (p = 0.018) compared to patients with lower values. Elevated z-score values were clearly associated with radiological proven progression. In contrast, baseline CTC count, CEA, and CA15-5 had no prognostic impact on the outcome of patients in the analyzed cohort.
This proof of principle study demonstrates the prognostic impact of ctDNA levels detected with mFAST-SeqS as a very fast and cost-effective means to assess the ctDNA fraction without prior knowledge of the genetic landscape of the tumor. Furthermore, mFAST-SeqS-based ctDNA levels provided an early means of measuring treatment response.
All authors have declared no conflicts of interest.