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 (1-10%). There was no significant relationship between ER% and corresponding SUVmax values (n = 34, r = 0.210, p = 0.233). There was a significant relationship between SUVmax and ER IHC intensity (n = 34, p = 0.044). Two positive biopsies (5.5%, 1+ and 95%, 3+) were negative on FES-PET performed after biopsy (42 and 61 days, respectively). Two positive biopsies (5.5%, 1-2+ and 100%, 3+) were negative on FES-PET performed prior to biopsy (9 and 49 days, respectively). ROC analysis determined SUVmax thresholds ≥1.4 accurately predict ER IHC positive status while retaining 100% specificity. An SUVmax threshold of ≥1.4 showed an AUC of 0.938, sensitivity of 87.5%, and overall accuracy of 88.24%. Six cases were not detected by the SUVmax ≥1.4 threshold and displayed an average ER% of 34.3±49.1 (two with no staining, two with 1+ staining, and two with 3+ staining). The remaining 28 cases that tested positive by SUVmax threshold displayed an average ER% of 78.6±25.1. Conclusion: Here we present one of the largest FES-PET IHC correlation studies to date. We show that FES-PET SUVmax magnitude is positively correlated with ER IHC staining intensity and that SUVmax thresholds lower than previously reported provide excellent ER classification in a heterogenous breast cancer cohort. Despite lower thresholds, FES-PET sensitivity and accuracy aligns with established values, which may provide more accurate classification and additional treatment options. In clinical practice, FES-PET will continue to provide critical adjunct information and may advance non-invasive receptor characterization strategies. Citation Format: E. T. Strand, C. Ferguson, E. M. Michaels, A. A. Lokhandwala, V. I. Bossuyt, S. A. Wander, S. G. Harrington. Linking PET to Pathology: FES SUVmax Aligns with ER IHC and Accurately Classifies ER at Reduced Cutoffs 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 PS1-06-29.
Strand et al. (Tue,) studied this question.