Abstract PS1-06-29: Linking PET to Pathology: FES SUVmax Aligns with ER IHC and Accurately Classifies ER at Reduced Cutoffs

Abstract Background: Breast cancer is the second leading cause of death for women in the United States.1 Breast cancer subtyping and receptor expression analysis by immunohistochemistry (IHC) is critical in determining treatment strategy. 18F-16α-Fluoroestradiol (FES) positron emission tomography (PET) allows for noninvasive characterization of the estrogen receptor (ER) in patients with inaccessible biopsy sites, multiple lesions, or non-diagnostic pathology results. Though prior literature has shown FES-PET SUVmax thresholds of 1.5-2.0 provide accurate classification of ER positivity, such studies are subject to very small sample sizes and atypical analytical workflows.2,3,4 There remain limited data on the degree of FES uptake, measured by SUVmax, as a function of ER expression in biopsy samples. Methods: Via a retrospective single center review, we evaluated 98 breast cancer patients who underwent FES-PET-CT or FES-PET-MR from December 2023 to July 2025. We selected patients with biopsy ER IHC data within a +/-90-day window from FES-PET. Patients were excluded if surgical excision was performed on the biopsied site prior to FES-PET. ER IHC data was recorded, including % of cells staining (ER%) and ER staining intensity (1, 2, or 3+). SUVmax values of each biopsy site were analyzed via simple 3D ROI by a board-certified nuclear radiologist. Relationships between SUVmax and ER% were analyzed using Spearman rank correlation. SUVmax and ER staining intensity were compared using Kruskal-Wallis analysis. Receiver Operating Characteristic analysis determined SUVmax thresholds to predict ER IHC positive status (defined as ≥1% of cells with nuclear staining). Statistical analysis was carried out using Python (Pandas, Numpy, Scipy, Matplotlib, and Seaborn packages). Results: 32 patients with breast cancer and corresponding ER IHC who underwent FES-PET imaging were included, with a total of 34 biopsies performed within the cohort (22 before FES-PET, 12 after FES-PET). Biopsies included 13 (38.2%) breast, 7 (20.6%) locoregional, and 14 (41.2%) metastatic sites. Average time from biopsy to FES-PET was 13.8±34.6 days. Among 34 biopsies, 94.1% were ER IHC positive (average ER% 70.8±34.2%, 17 (50.0%) 3+). Three biopsies were ER low-positive on IHC (1-