[ 18 F] Fluoroestradiol PET/CT to guide second-line treatment decision-making in patients with estrogen receptor–positive, HER2-negative advanced breast cancer after progression on first-line aromatase inhibitor and CDK4/6 inhibitor: Primary results of ESTROTIMP.

1077 Background: Despite availability of novel endocrine treatment (ET) options for patients with ER+ HER2- ABC, many patients experience early disease progression under 2 nd line ET-based regimen after AI+CDK4/6i, underscoring a significant rate of endocrine resistance. Timely identification of endocrine-refractory disease at progression under 1 st line is critical to optimize treatment selection and consider non-ET strategies, such as antibody-drug conjugates or chemotherapy. FES PET/CT enables a non-invasive, whole-body assessment of ER expression; absent or heterogeneous FES uptake may indicate ER loss or downregulation, key mechanisms of resistance. Our objective was to evaluate the impact of FES PET/CT on 2 nd line treatment decisions. Methods: In this non-randomized prospective multicenter trial (NCT05486182), patients with ER+ HER2- ABC progressing on 1 st line AI+CDK4/6i underwent standard-of-care FDG PET/CT followed by FES PET/CT. Oncologists prospectively documented therapeutic management plans, before and after FES PET/CT. Patients rated pain and apprehension for FES PET/CT vs. biopsy on a Visual Analogue Scale. Primary endpoint was the proportion of patients with a therapeutic management change after FES PET/CT, and primary objective was to demonstrate that at least 10% of patients had their therapeutic management changed after FES PET/CT (Wald test). Results: Of 153 patients enrolled, 129 were evaluable for the primary endpoint. When compared with FDG PET/CT, FES uptake was classified as “all lesions ER+” in 65 (50%), “mixed ER+/- lesions” in 38 (30%), and “all lesions ER-” in 25 (19%) patients. Therapeutic management was changed based on incorporation of FES PET/CT results in 46/129 patients (35.7%; 96% CI [27.0-44.3], p