Cell-free DNA and circulating tumor cells: Comprehensive liquid biopsy analysis in advanced breast cancer

Giovanna Rossi, Zhaomei Mu, Alfred W. Rademaker, Laura K. Austin, Kimberly S. Strickland, Ricardo Lima Barros Costa, Rebecca J. Nagy, Vittorina Zagonel, Timothy J. Taxter, Amir Behdad, Firas H. Wehbe, Leonidas C. Platanias, William J. Gradishar, Massimo Cristofanilli*

*Corresponding author for this work

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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 ctDNA 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 ¼ 0.021 and P ¼ 0.0004, respectively); %ctDNA < 0.5 versus 0.5 (P ¼ 0.003 and P ¼ 0.012); number of alterations < 2 versus 2 (P ¼ 0.059 borderline and P ¼ 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.

Original languageEnglish (US)
Pages (from-to)560-568
Number of pages9
JournalClinical Cancer Research
Volume24
Issue number3
DOIs
StatePublished - Feb 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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