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


Journal

JCO precision oncology
ISSN: 2473-4284
Titre abrégé: JCO Precis Oncol
Pays: United States
ID NLM: 101705370

Informations de publication

Date de publication:
06 2021
Historique:
received: 24 08 2020
revised: 10 01 2021
accepted: 21 04 2021
entrez: 17 6 2021
pubmed: 18 6 2021
medline: 18 6 2021
Statut: epublish

Résumé

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. 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. 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. 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.

Identifiants

pubmed: 34136741
doi: 10.1200/PO.20.00345
pii: PO.20.00345
pmc: PMC8202557
doi:

Substances chimiques

Circulating Tumor DNA 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Pagination

943-952

Subventions

Organisme : NCI NIH HHS
ID : R01 CA207468
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States

Informations de copyright

© 2021 by American Society of Clinical Oncology.

Déclaration de conflit d'intérêts

Massimo Cristofanilli Honoraria: Pfizer, Foundation Medicine Consulting or Advisory Role: Novartis, CytoDyn, Lilly, Foundation Medicine, Menarini Research Funding: Lilly, Angle, Merck No other potential conflicts of interest were reported.Massimo Cristofanilli Honoraria: Pfizer, Foundation Medicine Consulting or Advisory Role: Novartis, CytoDyn, Lilly, Foundation Medicine, Menarini Research Funding: Lilly, Angle, Merck No other potential conflicts of interest were reported.

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Auteurs

Lorenzo Gerratana (L)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.
Department of Medicine, University of Udine, Udine, Italy.
Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy.

Andrew A Davis (AA)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.
Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO.

Qiang Zhang (Q)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

Debora Basile (D)

Department of Medicine, University of Udine, Udine, Italy.
Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy.

Giovanna Rossi (G)

Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA.
Breast International Group (BIG), Brussels, Belgium.

Kimberly Strickland (K)

Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA.
Novant Health Cancer Institute, Charlotte, NC.

Alessandra Franzoni (A)

Institute of Human Genetics, ASUFC University Hospital, Udine, Italy.

Lorenzo Allegri (L)

Department of Medicine, University of Udine, Udine, Italy.

Zhaomei Mu (Z)

Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA.

Youbin Zhang (Y)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

Lisa E Flaum (LE)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

Giuseppe Damante (G)

Department of Medicine, University of Udine, Udine, Italy.
Institute of Human Genetics, ASUFC University Hospital, Udine, Italy.

William John Gradishar (WJ)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

Leonidas C Platanias (LC)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

Amir Behdad (A)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Department of Pathology, Northwestern University, Chicago, IL.

Hushan Yang (H)

Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA.

Fabio Puglisi (F)

Department of Medicine, University of Udine, Udine, Italy.
Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy.

Massimo Cristofanilli (M)

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

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