The prognostic value of circulating cell-free DNA in breast cancer: A meta-analysis

Circulating cell-free DNA (cfDNA) isolated from plasma or serum by noninvasive procedures can serve as a "liquid biopsy" and has potential as a biomarker for the tumor burden and survival prediction of breast cancer (BC). However, its prognostic value in patients with BC is currently under debate. The aim of this meta-analysis was to investigate the relationship between cfDNA and survival outcome. We systematically searched PubMed, Embase, and Science Citation Index electronic databases for studies about the prognostic utility of cfDNA in patients with BC. The clinical characteristics, relapse/disease-free survival (RFS/DFS), and overall survival (OS) data were extracted from the eligible studies. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated and pooled with a fixed-effects model using the Stata12.0 software. Subgroup and sensitivity analyses were also performed. This meta-analysis included a total of 10 eligible studies and 1127 patients with BC. The pooled HR with 95% CI showed strong associations between cfDNA and OS (HR = 2.41, 95% CI, 1.83-3.16) along with DFS/RFS (HR = 2.73, 95% CI, 2.04-3.67) in patients with BC. Although publication bias was found in the studies regarding RFS/DFS, further trim and fill analysis revealed that the adjusted HR would be 2.53 (95% CI, 1.83-3.51), which is close to the original HR. Subgroup analyses confirmed the role of cfDNA as a strong prognostic marker in patients with BC, regardless of cfDNA analysis, sampling time, sample source, detection method, tumor stage, sample size, or area. Our meta-analysis indicates that cfDNA is a strong predictive and prognostic marker in patients with BC.