Head-to-Head comparison of [18F]FES and [18F]FDG PET/CT in breast cancer patients: has a new era come?

Purpose: This review systematically compared, in a head-to-head manner, the diagnostic and prognostic performance of [18F]FDG and [18F]FES PET/CT in breast cancer (BC) patients. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases up to January 2025, without temporal limitations or restrictions on the number of patients in the included studies, to identify relevant articles comparing the diagnostic value of [18F]FDG and [18F]FES PET in BC patients. Selected imaging studies were analyzed using a modified version of the Critical Appraisal Skills Programme checklist dedicated to systematic reviews. Results: A total of 20 papers were evaluated. Based on the CASP analysis, the quality of the study was variable. Totally, 806 patients affected by BC underwent both [18F]FDG and [18F]FES PET. Different setting of disease were considered, such as staging/diagnostic and prognostic value. In the initial staging of disease, [18F]FES PET/CT seemed to be more accurate than [18F]FDG. In the prognostic field, [18F]FES expression was a positive factor for the better prognosis, in particular when the amount of [18F]FDG uptake was low. [18F]FES seemed to be promising as a molecular agent in patients affected by invasive lobular BC. Conclusion: These findings underscore the potential of [18F]FES as a complementary imaging biomarker to [18F]FDG, advocating for further studies to standardize PET metrics and refine their combined clinical utility.