They commonly occur in relapsed metastatic disease, and are possibly more frequent after treatment with aromatase inhibitors.7,8,17 These mutations induce constitutive receptor activity and have been identified as a mechanism of resistance to estrogen-depriving therapies, while patients might still benefit from selective estrogen receptor degradation (SERD) treatment, for example fulvestrant. Here, ESR1 is linked to metastatic neoplasm.