Circulating free DNA integrity and concentration as independent prognostic markers in metastatic breast cancer
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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.
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.
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.
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.
KeywordsMetastatic breast cancer Circulating DNA concentration Circulating DNA integrity Circulating tumor cells Prognostic marker
Area under the curve
Circulating free or cell-free DNA integrity
Circulating free or cell-free DNA
Circulating tumor cell
Integrated prediction errors
Metastatic breast cancer
National Center for Tumor Diseases, Heidelberg, Germany
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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