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

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

A Letter to the Editor to this article was published on 26 February 2018

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.

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Abbreviations

AUC:

Area under the curve

BL:

Baseline

cfDI:

Circulating free or cell-free DNA integrity

cfDNA:

Circulating free or cell-free DNA

CI:

Confidence interval

CTC:

Circulating tumor cell

HR:

Hazard ratio

IPE:

Integrated prediction errors

MBC:

Metastatic breast cancer

NCT:

National Center for Tumor Diseases, Heidelberg, Germany

PFS:

Progression-free survival

OS:

Overall survival

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Acknowledgements

We thank the study participants and all our colleagues who helped us with patient recruitment, blood collection, and processing. The study has been supported by cellgene.

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Authors and Affiliations

  1. Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Jie Cheng, Harald Surowy, Katarina Cuk & Barbara Burwinkel

  2. Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany

    Jie Cheng, Harald Surowy, Katarina Cuk & Barbara Burwinkel

  3. Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Tim Holland-Letz

  4. Department of Gynecology and Obstetrics, University Women’s Clinic, Heidelberg, Germany

    Markus Wallwiener, Sarah Schott, Christof Sohn & Andreas Schneeweiss

  5. National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany

    Markus Wallwiener & Andreas Schneeweiss

  6. Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Andreas Trumpp

  7. Hi-STEM-Heidelberg Institute for Stem Cell Technology and Experimental Medicine, GmbH, Heidelberg, Germany

    Andreas Trumpp

  8. Department of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Klaus Pantel

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  1. Jie Cheng
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Correspondence to Jie Cheng.

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Cheng, J., Holland-Letz, T., Wallwiener, M. et al. Circulating free DNA integrity and concentration as independent prognostic markers in metastatic breast cancer. Breast Cancer Res Treat 169, 69–82 (2018). https://doi.org/10.1007/s10549-018-4666-5

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  • DOI: https://doi.org/10.1007/s10549-018-4666-5

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