ESR1 and breast cancer: Given the continued challenge in treatment of ERα+breast cancer (especially in the advanced, drug-resistant setting),many therapies targeting ERα are being developed and investigated.45 However, in preclinical models, even optimizedSERDs and PROTACs targeting ERα are largely cytostatic and failto induce dramatic tumor regression when used as single agents.14−16,28,32 When used in combination with inhibitors of CDK4/6, PI3K, or AKTsome regression may be achieved in moderately sized tumors (100–300mm3),14−16,32 but complete tumoreradication is not observed.