Untargeted assessment of tumor fractions in plasma for monitoring and prognostication from metastatic breast cancer patients undergoing systemic treatment

Christoph Suppan, Iva Brcic, Verena Tiran, Hannah D. Mueller, Florian Posch, Martina Auer, Erkan Ercan, Peter Ulz, Richard J Cote, Ram H. Datar, Nadia Dandachi, Ellen Heitzer, Marija Balic

Research output: Contribution to journalArticle

Abstract

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. In metastatic breast cancer patients (n = 29), tumor fractions in plasma were assessed using the untargeted mFAST-SeqS method from 127 serial blood samples. Resulting z-scores for the ctDNA 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 survival (p = 0.014) and progression-free survival (p = 0.018) compared to patients with lower values. Elevated z-score values were clearly associated with radiologically proven progression. The baseline CTC count, carcinoembryonic antigen (CEA), and cancer antigen (CA)15-5 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.

Original languageEnglish (US)
Article number1171
JournalCancers
Volume11
Issue number8
DOIs
StatePublished - Aug 1 2019

Fingerprint

Breast Neoplasms
Neoplasms
DNA
Therapeutics
Circulating Neoplastic Cells
Carcinoembryonic Antigen
Tumor Biomarkers
Disease-Free Survival
Cell Count
Antigens
Costs and Cost Analysis
Survival

Keywords

  • Cell free circulating tumor DNA (ctDNA)
  • Circulating tumor cells (CTCs)
  • Metastatic breast cancer (MBC)
  • MFAST-SeqS
  • Prognosis
  • Treatment response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Untargeted assessment of tumor fractions in plasma for monitoring and prognostication from metastatic breast cancer patients undergoing systemic treatment. / Suppan, Christoph; Brcic, Iva; Tiran, Verena; Mueller, Hannah D.; Posch, Florian; Auer, Martina; Ercan, Erkan; Ulz, Peter; Cote, Richard J; Datar, Ram H.; Dandachi, Nadia; Heitzer, Ellen; Balic, Marija.

In: Cancers, Vol. 11, No. 8, 1171, 01.08.2019.

Research output: Contribution to journalArticle

Suppan, C, Brcic, I, Tiran, V, Mueller, HD, Posch, F, Auer, M, Ercan, E, Ulz, P, Cote, RJ, Datar, RH, Dandachi, N, Heitzer, E & Balic, M 2019, 'Untargeted assessment of tumor fractions in plasma for monitoring and prognostication from metastatic breast cancer patients undergoing systemic treatment', Cancers, vol. 11, no. 8, 1171. https://doi.org/10.3390/cancers11081171
Suppan, Christoph ; Brcic, Iva ; Tiran, Verena ; Mueller, Hannah D. ; Posch, Florian ; Auer, Martina ; Ercan, Erkan ; Ulz, Peter ; Cote, Richard J ; Datar, Ram H. ; Dandachi, Nadia ; Heitzer, Ellen ; Balic, Marija. / Untargeted assessment of tumor fractions in plasma for monitoring and prognostication from metastatic breast cancer patients undergoing systemic treatment. In: Cancers. 2019 ; Vol. 11, No. 8.
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AU - Auer, Martina

AU - Ercan, Erkan

AU - Ulz, Peter

AU - Cote, Richard J

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AB - 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. In metastatic breast cancer patients (n = 29), tumor fractions in plasma were assessed using the untargeted mFAST-SeqS method from 127 serial blood samples. Resulting z-scores for the ctDNA 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 survival (p = 0.014) and progression-free survival (p = 0.018) compared to patients with lower values. Elevated z-score values were clearly associated with radiologically proven progression. The baseline CTC count, carcinoembryonic antigen (CEA), and cancer antigen (CA)15-5 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.

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