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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2018

01-05-2018 | Clinical trial

Circulating free DNA integrity and concentration as independent prognostic markers in metastatic breast cancer

Authors: Jie Cheng, Tim Holland-Letz, Markus Wallwiener, Harald Surowy, Katarina Cuk, Sarah Schott, Andreas Trumpp, Klaus Pantel, Christof Sohn, Andreas Schneeweiss, Barbara Burwinkel

Published in: Breast Cancer Research and Treatment | Issue 1/2018

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Abstract

Purpose

Non-invasive blood-based molecular markers have been investigated for cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA) variables have been shown to be putative markers in breast cancer prognosis.

Methods

Here, we investigated the potential prognostic ability of cfDNA concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after one cycle of therapy in metastatic breast cancer (MBC) patients.

Results

A significantly increased cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and decreased cfDNA concentration (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) in both repetitive DNA elements after one cycle of therapy was observed. A multiple Cox regression model indicated that cfDI and cfDNA concentration can serve as independent prognostic markers in patients at baseline with HR (95% CI) of 0.70 (0.48–1.01) for ALU cfDI, 0.63 (0.44–0.92) for LINE1 cfDI, 2.44 (1.68–3.53) for ALU cfDNA concentration, and 2.12 (1.47–3.06) for LINE1 cfDNA concentration and after one cycle of therapy with HR (95% CI) of 0.59 (0.42–0.84) for ALU cfDI, 0.51 (0.36–0.74) for LINE1 cfDI, 1.59 (1.31–1.92) for ALU cfDNA concentration, and 1.30 (1.17–1.45) for LINE1 cfDNA concentration, respectively. By comparing integrated prediction error of different models, cfDNA variables were shown to improve the prognostic power of the CTC status.

Conclusions

We hereby show that cfDNA variables, especially in combination with other markers, can serve as attractive prognostic markers for MBC patients at baseline and during the systematic therapy.
Appendix
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Metadata
Title
Circulating free DNA integrity and concentration as independent prognostic markers in metastatic breast cancer
Authors
Jie Cheng
Tim Holland-Letz
Markus Wallwiener
Harald Surowy
Katarina Cuk
Sarah Schott
Andreas Trumpp
Klaus Pantel
Christof Sohn
Andreas Schneeweiss
Barbara Burwinkel
Publication date
01-05-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-4666-5

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