Blood-based biomarkers like microRNAs, cell-free DNA and circulating tumor cells hold great promise as they are reproducible and easily accessible in cancer patients. Cell-free DNA variables, such as cell-free DNA concentrations (cfDNA conc) and cell-free DNA integrity (cfDI), have great potential as diagnostic and prognostic markers in breast cancer patients. Here we investigated the potential prognostic ability of cfDNA conc and cfDI in a prospective study cohort of metastatic breast cancer (MBC) patients.
Blood was collected for cfDNA extraction from patients when enrolled about to start the first cycle of systematic therapy at baseline (MBCBL) and after the first cycle of systematic therapy (MBC1C). cfDNA conc and cfDI in blood plasma were evaluated by measuring the short and long fragments of two repetitive DNA elements, ALU (ALU-111bp, ALU-260bp) and LINE1 (LINE1-97bp, LINE1-266bp), by quantitative PCR. In total, 268 patients were included in this study. cfDNA conc and cfDI was compared between these two groups. The prognostic ability of cfDNA variables was evaluated by univariate and multivariate Cox regression model.
A significant increase of cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and decrease of cfDNA conc (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) were observed between patients at MBCBL and patients at MBC1C. Multiple Cox regression model indicated that cfDI and cfDNA conc can be used as independent prognostic markers in patients after one cycle of therapy with odds ratio (OR) and 95% confidence interval (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 conc, 2.12 (1.47 - 3.06) for LINE1 cfDNA conc for overall survival. When four cfDNA variables were combined, it can reach an OR of 2.53 (1.77-3.62) for overall survival analysis of patients.
In summary, our results showed a decreased cfDNA conc and increased cfDI from the enrollment of the study to the first cycle of systematic therapy in MBC patients. cfDNA conc and cfDI can serve as independent prognostic markers in MBC patients after the first cycle of systematic therapy.
Clinical trial identification
Legal entity responsible for the study
Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany
The University Hospital of Heidelberg, Heidelberg, Germany; the German Cancer Research Center (DKFZ), Heidelberg, Germany
All authors have declared no conflicts of interest.