The Role of [18F]FES PET/CT in Breast Cancer Management: An Umbrella Review

Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer worldwide. Estrogen receptor (ER) status is a key determinant in the diagnosis and treatment of BC. Although immunohistochemistry (IHC) is the gold standard for ER assessment, it has limitations. This umbrella review aims to evaluate the role of 16α-18F-fluoro-17β-estradiol ([18F]FES) PET/CT as a non-invasive imaging tool for assessing ER expression and its implications in BC management. Methods: A comprehensive search was conducted in PubMed/MEDLINE and Cochrane Library for systematic reviews and meta-analyses published in the last decade. Studies eligible for inclusion evaluated the diagnostic accuracy and clinical utility of [18F]FES PET/CT in BC based on a predefined research question “What is the role of fluoroestradiol ([18F]FES) PET/CT in breast cancer?”. Data extraction and quality assessment were performed independently by two reviewers using the AMSTAR-2 tool. Results: Eight systematic reviews met the inclusion criteria. [18F]FES PET/CT demonstrated high sensitivity (81–94%) and specificity (78–95%) in detecting ER-positive lesions. It provided a real-time, whole-body assessment of ER expression, outperforming IHC in detecting functional ER activity. Additionally, [18F]FES PET/CT showed promise in predicting treatment response and guiding therapy decisions, particularly in metastatic settings. Conclusions: This review highlights the clinical value of [18F]FES PET/CT in BC management, offering a non-invasive alternative for ER assessment with high diagnostic accuracy. Its integration into clinical practice may enhance personalized treatment strategies for BC patients.