Among these mutated genes, we found a statistically significant enrichment of non-silent mutations in ESR1 and ARID1A for both cfDNA and tumor biopsies in 20 ER+/HER2− metastatic cancer patients when compared to 279 primary ER+/HER2− breast carcinomas published previously by The Cancer Genome Atlas (TCGA)25 (Bonferroni-corrected Fisher’s exact test, p = 1.46 × 10−8 and 2.58 × 10−2 respectively). This evidence concerns the gene ESR1 and breast carcinoma.