Background: Circulating tumor DNA (ctDNA) is a non-invasive biomarker for evaluating cancer prognosis. The aim of this study was to analyze the genomic profile of circulating tumor DNA (ctDNA) in breast cancer patients, and evaluate its clinical implications.
Methods: Targeted sequencing of ctDNA was performed in 38 patients using commercially available Oncomine Breast cfDNA panel. Whole exome sequencing was performed on matched tumor DNA (n=20). Survival analysis and response to chemotherapy in the study population were evaluated. The detected genomic variants were validated and serially monitored with droplet digital polymerase chain reaction (ddPCR) in 5 patients.
Results: At least one variant or copy number alteration was detected in the ctDNA of 31 of 38 (82%) breast cancer patients, with the most common variants being in TP53 (50%), PIK3CA (15%) and ESR1 (14%). When comparing genomic profiles of ctDNA and those of matched tumor DNA in 20 patients, the concordance rate was 9.7% among positives. The patients with variants in TP53 showed significantly poorer overall survival than those without [hazard ratio (HR) =3.90, 95% confidence interval (CI): 1.10-13.84, P=0.035] and its impact was also statistically significant in multivariate analysis with breast cancer subtype included. In serially monitored results, changes in the allele frequency of somatic variants (PI3KCA, TP53) of ctDNA were found to be reflective of response to chemotherapy.
Conclusions: The genomic profile of ctDNA reflects and provides additional information to the tumor DNA genome profile. Follow-up monitoring of mutations detected in ctDNA is useful in the clinical management of breast cancer patients.
Keywords: Breast cancer; circulating tumor DNA (ctDNA); high-throughput nucleotide sequencing.
2022 Annals of Translational Medicine. All rights reserved.