Clinical significance of gene mutation in ctDNA analysis for hormone receptor-positive metastatic breast cancer

Purpose In this study, we aim to investigate the mutation spectrum of circulating tumor DNA among hormone receptor-positive metastatic breast cancer (HR-MBC) patients using ultradeep targeted resequencing. In addition, we also evaluate the correlation of mutations detected from this study with progression-free survival (PFS). Materials and methods A total of 56 HR-MBC patients were enrolled. Cell-free DNA (cfDNA) was extracted from plasma and sequenced by using Oncomine Breast cancer cfDNA assay in this study. Result Concentration of cfDNA is correlated with a number of metastatic organs and serum CEA levels (Spearman’s rank correlation p = 0.0018, p = 0.0015 respectively). Cases with high cfDNA levels (≥ 2.6 ng/μl of plasma) showed worse progression-free survival (PFS) and overall survival compared with cases with low cfDNA levels ( p = 0.043 and 0.046, respectively). Among these patients, 29 patients (51.7%) have TP53 mutations, 12 patients (30.3%) have PIK3CA mutations, and 9 patients (16.0%) have ESR1 mutations. Acquisition of ESR1 mutation increased according to the lines of hormone therapy. In addition, patients with ESR1 mutation showed shorter PFS than those without mutation (log-rank p = 0.047). In the multivariate analysis, ESR1 mutation and cfDNA concentration were significant for PFS ( p = 0.027 and 0.006, respectively). In conclusion, assessment of ESR1 mutation and cfDNA concentration could be useful in predicting prognosis for HR-MBCs.