Abstract Background: 18F-Fluoroestradiol (FES) positron emission tomography (PET) is approved for non-invasive detection of estrogen receptor (ER)-positive breast cancer (BC) and recent updates to the National Comprehensive Cancer Center Network clinical practice guidelines include FES-PET for staging recurrent/metastatic ILC. Given the wide range of FES-PET indications, we retrospectively reviewed the management of ER+ BC patients after FES-PET at Mayo Clinic. Methods: We identified ER+ BC patients who underwent FES-PET from April 2021 to June 2025 across the Mayo Clinic. BC context at the time of FES-PET requisition was categorized as early (EBC), locally recurrent (LRBC), or metastatic (MBC). Management changes were classified as either affecting BC or non-BC care (not mutually exclusive). For pts who underwent 18F-flurodeoxyglucose (FDG) PET-CT and had a discrepant result with FES-PET, we assessed the clinical impact of these discrepancies. Finally, we examined the change in clinical management when FES-PET was ordered to investigate rising tumor markers CA 15-3 or CA 27.29. Results: 166 pts underwent ≥1 FES-PET scan. At diagnosis, 57% had invasive lobular carcinoma (ILC), 33% invasive ductal carcinoma (IDC), and 5.4% mixed histology. ER expression ≥ 50% was observed in 81.4% and 1.2% were HER2+. Overall, FES-PET led to a change in management in 54.5% (n=90) of pts with 43.0% (n=71) experiencing a change in BC care and 16.4% (n=27) in non-BC care. Changes in BC care occurred in 36% of EBC, 68% of LRBC, and 43.7% of MBC. The most common BC management changes after FES-PET were change in treatment strategy in 23.6% (n=39), additional BC-related imaging including further FES-PET scans in 23.0% (n=38), upstaging in 10.3% (n=17), change in surgical planning in 10.3% (n=17), local therapy in 4.2% (n=7), and biopsy avoidance in 3% (n=5). Surgical planning changes were mostly deciding to proceed with curative intent surgery (n=11), though some surgeries were aborted upon FES-PET upstaging (n=6). Non-BC management changes included additional imaging to evaluate incidental findings in 11.5% (n=19) and procedures in 6.7% (n=11), including 5 biopsies, 2 bronchoscopies, 2 endoscopies, 1 hysterectomy, and 1 cholecystectomy. FDG/FES discordancy was observed in 22.3% of the overall population (n=37). The most common pattern was FDG-/FES+ (n=19), leading to upstaging of BC in 8 and the sole use of FES-PET for future restaging in 13 BC patients. The second most common pattern was FDG+/FES- (n=18), attributed to non-BC related FDG uptake in 11 (false-positive FDG) or post-treatment ER loss in 7. Three FDG+/FES- patients were found to have additional cancers: two non-small cell lung cancers and one lymphoma. Non-malignant causes of false positive FDG were inflammation (n=3), silicone implants (n=1), thymic hyperplasia (n=1), and unknown (n=5). Six patients initially upstaged with FDG-PET imaging proceeded to curative-intent surgery after negative FES-PET confirmatory scans (FDG+/FES-). When FES-PET was ordered to investigate rising CA 15-3 or CA 27.29 tumor markers, this led to upstaging/progression in 3 of 21 cases (1 EBC, 2 MBC). The mean tumor marker increase was 57.0% in patients with upstaging/progression versus 19.0% in those without (p=0.02, two-tailed Student’s t-test). Conclusions: FES-PET altered clinical management in approximately half of BC cases in this study. Changes in BC-specific management were most frequent in LRBC, followed by MBC and EBC. One in six patients had a non-BC clinical management change after FES-PET. FDG/FES discordance provided value in upstaging FDG non-avid cancers and downstaging FDG-avid lesions unrelated to BC, influencing curative treatment decisions. FES-PET ordered for rising tumor markers rarely changed management, though larger tumor marker increases were associated with upstaging or progression. Citation Format: N. Wiest, K. Bullock, T. Pai, M. Kornas, B. McKinley, E. Parent, P. Advani. FES-PET imaging in estrogen receptor-positive breast cancer: implications for clinical management abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-06-16.
Wiest et al. (Tue,) studied this question.