Detection of TP53/PIK3CA Mutations in Cell-Free Plasma DNA From Metastatic Breast Cancer Patients Using Next Generation Sequencing

Background: Circulating tumor DNA (ctDNA) within a liquid biopsy is a promising marker for genotyping metastatic tumors. Materials and Methods: We performed next generation whole exon sequencing of TP53 and PIK3CA genes, which are the 2 most common genetic alterations in breast cancer, in plasma DNA (pDNA) of 17 metastatic breast cancer (MBC) patients and in tumor DNA (tDNA) from their primary tumors. Results: We identified 11 mutations (6 in TP53 and 5 in PIK3CA) in tDNA from 8 patients (47%) and 13 mutations (6 in TP53 and 7 in PIK3CA) in pDNA from 7 patients (41%). Six mutations in pDNA were also identified in tDNA but seven were not. Six MBC patients with TP53 and/or PIK3CA mutations in pDNA had a significantly worse survival rate (P < .05) after recurrence than that of the other 8 MBC patients without these mutations. Carcinoembryonic antigen and cancer antigen 15-3 levels did not correlate with prognosis (P = .675 and P = .877, respectively). Conclusion: These results suggest that mutations in ctDNA can be detected with next generation sequencing in MBC patients and could be a more useful prognostic factor for survival after recurrence than conventional tumor markers.