High Cell-Free DNA Integrity Is Associated with Poor Breast Cancer Survival

SIMPLE SUMMARY: A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and BC survival is already recognized, studies on the prognostic value of cfDI have had contradictory results. The aim of this study was to investigate the prognostic potential of cfDConc and cfDI in Eastern Finnish BC cases with a non-metastatic disease. While the prognostic value of cfDConc remained non-significant in our analyses, high cfDI was an independent prognostic factor for poor overall survival (OS) and breast cancer-specific survival (BCSS). Inclusion of cfDI in the multivariate logistic regression model improved the predictive performance of the model, thus suggesting that the combined use of traditional tumor features and liquid biopsy could help to discriminate BC patients with poor OS and BCSS more accurately at the time of diagnosis. ABSTRACT: Background: A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA (cfDNA) and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and poor survival is already recognized, studies on the prognostic value of cfDI have had contradictory results. Here, we provide further evidence to support the use of cfDI as a potential biomarker. Methods: We selected 204 Eastern Finnish BC cases with non-metastatic disease and isolated cfDNA from the serum collected at the time of diagnosis before any treatment was given. The cfDConc and cfDI were measured with a fluorometer and electrophoresis and analyzed with 25 years of survival data. Results: High cfDConc was not an independent prognostic factor in our analyses while high cfDI was found to be an independent prognostic factor for poor OS (p = 0.020, hazard ratio (HR) = 1.57, 95% confidence interval (CI) 1.07–2.29, Cox) and BCSS (p = 0.006, HR = 1.93, 95% CI 1.21–3.08)). Inclusion of cfDI in the multivariate logistic regression model improved the predictive performance. Conclusions: Our results show high cfDI is an independent prognostic factor for poor OS and BCSS and improves the predictive performance of logistic regression models, thus supporting its prognostic potential.