Numbers of sequenced metastatic and primary breast cancer samples and reported ESR1 LBD point mutations (*) are indicated. The dashed lines indicate primary tumors that were sequenced subsequently to the detection of the ESR1 LBD mutation in their matched metastatic specimens. The ER+ BC cohort from Jeselsohn’s study included upfront 37 matched ER+ metastatic and primary sample pairs, of which in 2 of these pairs (#) ESR1 LBD mutations were detected in the metastatic but not in the primary tumors. Abbreviations: BC, breast cancer; BOLERO-2, Breast cancer trials of OraL EveROlimus-2; Met, metastatic samples; MI-ONCOSEQ, the MIchigan ONCOlogy SEQuencing program; MSKCC, Memorial Sloan Kettering Cancer Center; PDXs, Patient-derived xenografts.