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Breast Cancer Res Treat. 2018 May;169(1):69-82. doi: 10.1007/s10549-018-4666-5. Epub 2018 Jan 16.

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

Author information

1
Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. chengjiehmzx@126.com.
2
Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany. chengjiehmzx@126.com.
3
Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Department of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany.
5
National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
6
Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
8
Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
Hi-STEM-Heidelberg Institute for Stem Cell Technology and Experimental Medicine, GmbH, Heidelberg, Germany.
10
Department of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

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.

KEYWORDS:

Circulating DNA concentration; Circulating DNA integrity; Circulating tumor cells; Metastatic breast cancer; Prognostic marker

PMID:
29340881
DOI:
10.1007/s10549-018-4666-5
[Indexed for MEDLINE]

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