Research Papers:

Cell-free circulating DNA integrity is an independent predictor of impending breast cancer recurrence

Jie Cheng, Katarina Cuk, Jörg Heil, Michael Golatta, Sarah Schott, Christof Sohn, Andreas Schneeweiss, Barbara Burwinkel _ and Harald Surowy

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Oncotarget. 2017; 8:54537-54547. https://doi.org/10.18632/oncotarget.17384

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Jie Cheng1,2, Katarina Cuk1,2, Jörg Heil3, Michael Golatta3, Sarah Schott3, Christof Sohn3, Andreas Schneeweiss3,4, Barbara Burwinkel1,2,* and Harald Surowy1,2,*

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

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

3Department of Gynecology and Obstetrics, University Women’s Clinic, Heidelberg, Germany

4National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany

*These authors have share the last authorship

Correspondence to:

Barbara Burwinkel, email: [email protected]

Keywords: breast cancer, recurrence, circulating DNA integrity, biomarker

Received: October 11, 2016     Accepted: March 26, 2017     Published: April 24, 2017


Non-invasive blood-based molecule markers are evaluated as promising biomarkers these days. Here we investigated the potential of cell-free circulating DNA Integrity (cfDI) as blood-based marker for the prediction of recurrence during the follow-up of breast cancer patients within a prospective study cohort. cfDI was determined in plasma of 212 individuals, by measuring ALU and LINE1 repetitive DNA elements using quantitative PCR. A significant decrease of cfDI in recurrent breast cancer patients was observed. The group of patients who had impending recurrence during the follow-up had significant lower cfDI compared to the group of non-recurrent patients (P < 0.001 for ALU and LINE1 cfDI). cfDI could differentiate recurrent breast cancer patients from non-recurrent breast cancer subjects (area under the curve, AUC = 0.710 for ALU and 0.704 for LINE1). Univariate and multivariate analysis confirmed a significant association of recurrence and cfDI. Breast cancer patients with a lower cfDI had a much higher risk to develop recurrence than the patients with a higher cfDI (P = 0.020 for ALU cfDI and P = 0.019 for LINE1 cfDI, respectively). Further we show that cfDI is an independent predictor of breast cancer recurrence. In combination with other molecular markers, cfDI might be a useful biomarker for the prediction for breast cancer recurrence in clinic utility. We propose that cfDI might also be useful for the prediction of recurrence during the follow-up of other cancers.

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