Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA.

Adult Aged Breast Neoplasms / blood Cell Count Circulating Tumor DNA / blood Disease Progression Female Humans Liquid Biopsy Middle Aged Neoplasm Metastasis Neoplastic Cells, Circulating / pathology Predictive Value of Tests Progression-Free Survival Real-Time Polymerase Chain Reaction Risk Assessment Risk Factors Time Factors

Circulating cell-free DNA (ccfDNA) Circulating tumour cell (CTC) Metastatic breast cancer (MBC) Prognosis

Journal

European journal of cancer (Oxford, England : 1990)

ISSN: 1879-0852

Titre abrégé: Eur J Cancer

Pays: England

ID NLM: 9005373

Informations de publication

Date de publication:
01 2019

Historique:

received: 05 06 2018

revised: 03 10 2018

accepted: 29 10 2018

pubmed: 12 12 2018

medline: 6 5 2020

entrez: 12 12 2018

Statut: ppublish

Résumé

Both circulating tumour cell (CTC) and total circulating cell-free DNA (ccfDNA) predict cancer patient prognosis. However, no study has explored the prognostic value of the combined use of CTC and ccfDNA. We aimed to investigate individual and joint effects of CTC and ccfDNA on clinical outcomes of metastatic breast cancer (MBC) patients. We collected 227 blood samples from 117 MBC patients. CTCs were enumerated using the CellSearch System. ccfDNAs were quantified by quantitative real-time polymerase chain reaction and Qubit fluorometer. The individual and joint effects of CTC and ccfDNA levels on patient progression-free survival (PFS) and overall survival (OS) were analysed using Cox proportional hazards models. Compared to patients with <5 CTCs, patients with ≥5 CTCs had a 2.58-fold increased risk of progression and 3.63-fold increased risk of death. High level of ccfDNA was associated with a 2.05-fold increased risk of progression and 3.56-fold increased risk of death. These associations remained significant after adjusting for other important clinical covariates and CTC/ccfDNA levels. CTC and ccfDNA levels had a joint effect on patient outcomes. Compared to patients with low levels of both CTC and ccfDNA, those with high levels of both markers exhibited a >17-fold increased death risk (P < 0.001). Moreover, longitudinal analysis of 132 samples from 22 patients suggested that the inconsistency between CTC level and outcome in some patients could possibly be explained by ccfDNA level. CTC and total ccfDNA levels were individually and jointly associated with PFS and OS in MBC patients.

Sections du résumé

BACKGROUND

METHODS

We collected 227 blood samples from 117 MBC patients. CTCs were enumerated using the CellSearch System. ccfDNAs were quantified by quantitative real-time polymerase chain reaction and Qubit fluorometer. The individual and joint effects of CTC and ccfDNA levels on patient progression-free survival (PFS) and overall survival (OS) were analysed using Cox proportional hazards models.

RESULTS

Compared to patients with <5 CTCs, patients with ≥5 CTCs had a 2.58-fold increased risk of progression and 3.63-fold increased risk of death. High level of ccfDNA was associated with a 2.05-fold increased risk of progression and 3.56-fold increased risk of death. These associations remained significant after adjusting for other important clinical covariates and CTC/ccfDNA levels. CTC and ccfDNA levels had a joint effect on patient outcomes. Compared to patients with low levels of both CTC and ccfDNA, those with high levels of both markers exhibited a >17-fold increased death risk (P < 0.001). Moreover, longitudinal analysis of 132 samples from 22 patients suggested that the inconsistency between CTC level and outcome in some patients could possibly be explained by ccfDNA level.

CONCLUSIONS

CTC and total ccfDNA levels were individually and jointly associated with PFS and OS in MBC patients.

Identifiants

DOI: 10.1016/j.ejca.2018.10.012 PMID: 30528798 PMC: PMC6347110

pubmed: 30528798

pii: S0959-8049(18)31451-5

doi: 10.1016/j.ejca.2018.10.012

pmc: PMC6347110

mid: NIHMS1515873

pii:

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

Sous-ensembles de citation

Pagination

133-143

Subventions

Organisme : NCI NIH HHS

ID : P30 CA056036

Pays : United States

Organisme : NCI NIH HHS

ID : R01 CA207468

Pays : United States

Informations de copyright

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