Multiple studies have now shown that the ESR1 LBD mutations can be successfully detected in the plasma of patients with metastatic ER + breast cancer.5,6 Patients with ER + metastatic breast cancer who received an aromatase inhibitor (AI) in the metastatic setting compared to AI naive patients had a higher prevalence of cfDNA ESR1 mutations.7 Moreover, patients with metastatic ER + breast cancer with detectable cfDNA ESR1 mutations had decreased progression free survival on subsequent treatment with an aromatase AI.6 This evidence concerns the gene ESR1 and breast cancer.