Although 18F-FES PET/CT imaging can assess ER occupancy to its ligand estrogen, it does not constitute formal proof that amcenestrant degrades ERs in tumors; however, our paired tumor biopsy analyses confirmed that amcenestrant achieved on-target activity (ER degradation/pathway inhibition) among women with metastatic ER+/HER2– breast cancer whose tumors carried multiple ESR1 mutations (Fig. 4a–d). This evidence concerns the gene ESR1 and breast carcinoma.