The assessment of circulating cell-free DNA as a diagnostic tool for breast cancer: an updated systematic review and meta-analysis of quantitative and qualitative ssays.

Objectives: This updated meta-analysis aimed to assess the diagnostic accuracy of circulating cell-free DNA (cfDNA) in breast cancer (BC).

Content: An extensive systematic search was performed in PubMed, Scopus, Embase, and Science Direct databases to retrieve all related literature. Various diagnostic estimates, including sensitivity (SE), specificity (SP), likelihood ratios (LRs), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (sROC) curve, were also calculated using bivariate linear mixed models.

Summary: In this meta-analysis, 57 unique articles (130 assays) on 4246 BC patients and 2,952 controls, were enrolled. For quantitative approaches, pooled SE, SP, PLR, NLR, DOR, and AUC were obtained as 0.80, 0.88, 6.7, 0.23, 29, and 0.91, respectively. Moreover, for qualitative approaches, pooled SE and SP for diagnostic performance were obtained as 0.36 and 0.98, respectively. In addition, PLR was 14.9 and NLR was 0.66. As well, the combined DOR was 23, and the AUC was 0.79.

Outlook: Regardless of promising SE and SP, analysis of LRs suggested that quantitative assays are not robust enough neither for BC confirmation nor for its exclusion. On the other hand, qualitative assays showed satisfying performance only for confirming the diagnosis of BC, but not for its exclusion. Furthermore, qualitative cfDNA assays showed a better diagnostic performance in patients at the advanced stage of cancer, which represented no remarkable clinical significance as a biomarker for early detection.