Resumen
ESR1 mutations in breast cancer are one of the mechanisms of resistance to aromatase inhibitors (AI). These mutations are common in metastatic breast cancer (MBC). In past reports, mutations in primary tumors were so rare that they were thought to occur de novo with AI therapy. Conversely, previous studies using droplet digital polymerase chain reaction (ddPCR) have suggested the existence of ESR1-mutant minor clones with low allele frequencies; however, no large-scale studies have been conducted. In this study, we attempted to detect ultra-rare ESR1 mutations in primary breast cancer tumors using locked nucleic acid (LNA)-clamp ddPCR, and 28 ESR1 mutations were found in 27 patients. Most of these mutations were minor clones with a variant allele frequency of <0.1% which may have been overlooked by conventional methods. LNA-clamp ddPCR can also be applied to detect other gene mutations, which would be very useful.