First reported in 1997 [4], these mutations have been recently described as (i) an acquired alteration, with a presence in primary tumour in less than 2% of cases [5, 6]; (ii) frequent, with a detection rate approximately 20% in metastases of HR+MBC patients progressing after endocrine therapy [7, 8]; and (iii) recurrent, with 4 hot-spot mutations (D538G, Y537S/N/C) contributing to 74% of all ESR1 acquired mutations [5]. Here, ESR1 is linked to neoplasm.