The strong pre-clinical data around MDM2 inhibition’s potential synthetic lethality role in ER +, GATA3mut ER + breast cancer led to the design of a phase II clinical trial using the MDM2 inhibitor milademetan plus fulvestrant in patients with ER +, HER2−, GATA3mut advanced breast cancer (NCT05932667), where the GATA3 mutation would be identified via sequencing the tumor and/or ctDNA. This evidence concerns the gene ESR1 and breast carcinoma.