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 Wehbe, Leonidas C Platanias, William J Gradishar, Massimo Cristofanilli*

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Citations (Scopus)

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

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Circulating Neoplastic Cells
Breast Neoplasms
Biopsy
DNA
Neoplasms
Disease-Free Survival
Survival
p53 Genes
Survival Analysis
Research Design
Retrospective Studies
Neoplasm Metastasis
Mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rossi, Giovanna ; Mu, Zhaomei ; Rademaker, Alfred W ; Austin, Laura K. ; Strickland, Kimberly S. ; Costa, Ricardo Lima Barros ; Nagy, Rebecca J. ; Zagonel, Vittorina ; Taxter, Timothy J. ; Behdad, Amir ; Wehbe, Firas ; Platanias, Leonidas C ; Gradishar, William J ; Cristofanilli, Massimo. / Cell-free DNA and circulating tumor cells : Comprehensive liquid biopsy analysis in advanced breast cancer. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 3. pp. 560-568.
@article{82f2d3c167364480b6b10da540a682f8,
title = "Cell-free DNA and circulating tumor cells: Comprehensive liquid biopsy analysis in advanced breast cancer",
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.",
author = "Giovanna Rossi and Zhaomei Mu and Rademaker, {Alfred W} and Austin, {Laura K.} and Strickland, {Kimberly S.} and Costa, {Ricardo Lima Barros} and Nagy, {Rebecca J.} and Vittorina Zagonel and Taxter, {Timothy J.} and Amir Behdad and Firas Wehbe and Platanias, {Leonidas C} and Gradishar, {William J} and Massimo Cristofanilli",
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Cell-free DNA and circulating tumor cells : Comprehensive liquid biopsy analysis in advanced breast cancer. / Rossi, Giovanna; Mu, Zhaomei; Rademaker, Alfred W; Austin, Laura K.; Strickland, Kimberly S.; Costa, Ricardo Lima Barros; Nagy, Rebecca J.; Zagonel, Vittorina; Taxter, Timothy J.; Behdad, Amir; Wehbe, Firas; Platanias, Leonidas C; Gradishar, William J; Cristofanilli, Massimo.

In: Clinical Cancer Research, Vol. 24, No. 3, 01.02.2018, p. 560-568.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cell-free DNA and circulating tumor cells

T2 - Comprehensive liquid biopsy analysis in advanced breast cancer

AU - Rossi, Giovanna

AU - Mu, Zhaomei

AU - Rademaker, Alfred W

AU - Austin, Laura K.

AU - Strickland, Kimberly S.

AU - Costa, Ricardo Lima Barros

AU - Nagy, Rebecca J.

AU - Zagonel, Vittorina

AU - Taxter, Timothy J.

AU - Behdad, Amir

AU - Wehbe, Firas

AU - Platanias, Leonidas C

AU - Gradishar, William J

AU - Cristofanilli, Massimo

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

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U2 - 10.1158/1078-0432.CCR-17-2092

DO - 10.1158/1078-0432.CCR-17-2092

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AN - SCOPUS:85041602617

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JO - Clinical Cancer Research

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