Clinical factors associated with circulating tumor DNA (ctDNA) in primary breast cancer

Noninvasive circulating tumor DNA (ct DNA ) can be used to predict breast cancer recurrence and prognosis. In this study, we detected 226 and 114 somatic variants in tumor DNA from 70 primary breast cancer ( PBC ) patients (98.59%) and ct DNA from 48 patients (67.61%), respectively. Gene frequencies of tumor DNA and ct DNA significantly correlated ( R 2 = 0.9532, P < 0.0001), and tumor‐derived variants were detectable in the blood of 43 patients. ct DNA was more often detected in locally advanced/metastatic and nonluminal patients. Multivariate analysis revealed that individual N stage ( P < 0.001) and hormone receptor (HR) status ( P = 0.001) could independently predict the detectability of tumor‐derived mutations in blood. The maximal variant allele frequency of ct DNA was significantly higher in patients with stage IV /M1 ( P = 0.0136) and stage T3/T4 ( P = 0.0085) cancers. Finally, clonal variants in tumor DNA were more easily traced in ct DNA than subclonal variants (84.62% vs 48.75%). In conclusion, ct DNA fragments concordant with tumor DNA can be consistently detected in the majority of tested PBC patients, which may enable noninvasive genomic profiling of PBC , particularly for patients with advanced‐stage tumors and positive HR status.