Diagnostic effectiveness of [18F]Fluoroestradiol PET/CT in oestrogen receptor-positive breast cancer: the key role of histopathology. Evidence from an international multicentre prospective study.

[ <sup>18</sup> F]Fluoroestradiol ([ <sup>18</sup> F]FES) PET/CT has been proposed as a tool for detecting the oestrogen receptor density in patients with metastatic breast cancer (BC) non-invasively across all disease localizations. However, its diagnostic potential in terms of the detection rate (DR) of metastases is unclear. In this study, we pitted this method against [ <sup>18</sup> F]FDG PET/CT and tried to identify predictors of the diagnostic superiority of the [ <sup>18</sup> F] FES-based method. From a multicentre database, we enrolled all patients with metastatic BC who had undergone both [ <sup>18</sup> F]FES PET/CT and [ <sup>18</sup> F]FDG PET/CT. Two readers assessed both images independently and used a patient-based (PBA) and lesion-based analysis (LBA) to calculate the DR. Pathology-related and clinical factors were tested as predictors of [ <sup>18</sup> F]FES PET/CT superiority using a multivariate model. 92 patients, bearing a total of 2678 metastases, were enrolled. On PBA, the DR of [ <sup>18</sup> F]FDG and [ <sup>18</sup> F]FES PET/CT was 97% and 86%, respectively (p = 0.018). On LBA, the [ <sup>18</sup> F]FES method proved more sensitive than [ <sup>18</sup> F]FDG PET/CT in lymph nodes, bone, lung and soft tissue (p < 0.01). This greater sensitivity was associated with lobular histology, both on PBA (Odds Ratio (OR) 3.4, 95%CI 1.0-12.3) and on LBA (OR 4.4, 95%CI 1.2-16.1 for lymph node metastases and OR 3.29, 95%CI 1.1-10.2 for bone localizations). The overall DR of [ <sup>18</sup> F]FES PET/CT appears to be lower than that of [ <sup>18</sup> F]FDG PET/CT on PBA. However, the [ <sup>18</sup> F]FES method, if positive, can identify more lesions than [ <sup>18</sup> F]FDG at most sites. The higher sensitivity of [ <sup>18</sup> F]FES PET/CT was associated with lobular histology