ESR1 and breast cancer: Aromatase inhibitors (AIs) are the standard of care as first-line treatment for postmenopausal women with oestrogen receptor positive (ER + ) advanced breast cancer (BC).1 However, the objective response rate to AIs in the metastatic setting is between 20%–40% and virtually all patients eventually relapse with AI-resistant disease.2,3 It is critical to understand the molecular drivers of the resistance to allow rational use of subsequent or concurrent therapy.