ESR1 and breast cancer: In preclinical studies, ARV-471 demonstrated potent degradation with significant anti-proliferative effects, and a Phase I study reported good tolerability and a clinical benefit rate of 40% in patients with R/R advanced ER+/HER2- breast cancer.350–352 Ongoing Phase II studies are assessing higher doses, showing promising efficacy, especially in patients with ESR1 mutations.352 Encouraged by these preliminary data, ARV-471 entered two pivotal Phase III trials.