Abstract PS1-12-01: Brain fes pet standardized uptake value association with esr1 and pik3ca genomic alterations

Abstract Objectives: Breast cancer (BC) is the second most common cancer linked to brain metastases(BM), with 70% of patients having estrogen receptor-positive (ER+) disease. Brain metastases represent a major clinical challenge, second in frequency only to those arising from lung cancer.[F18]-Fluoroestradiol ([F18]-FES) PET is an FDA-approved molecular imaging tool that targets ER with high specificity (>90%) and allows whole-body assessment of ER expression. BrainFES PET has shown promise as an adjunct diagnostic tool in BC BM. Liquid biopsies, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes, are emerging non-invasive diagnostic and monitoring tools. Our purpose was to combine FES PET with liquidbiopsy in a pilot cohort to assess the potential of this multi-modal biomarker in evaluatingresponse to endocrine and radiotherapy in patients with ER+ BC BM. Methods: Following informed consent, patients with ER+ BC and known or suspected BM who underwent dedicated brain FES PET/CT and blood ctDNA analysis were included in this IRB-approved prospective study. Clinical and demographic data were collected via chart review. Dedicated dynamic brain PET/CT acquisition was performed from 0-90 minutes. FES PET was co-registered to post-gadolinium contrast 3D T1 MRI. Two 10-mL blood samples were collected and analyzed using the Guardant360 next-generation sequencing platform to detect genetic alterations. Codon variants of ESR1 and PIK3CA mutations were analyzed, and mutant allele frequency was assessed for personalized treatment. The average maximum standardized uptake values (SUV) in ESR1- and PIK3CA-positive and ESR1- and PIK3CA-negative groups were compared separately. Mann-Whitney and Spearman correlation tests were performed. Results: Nine patients with FES-positive lesions were stratified by PIK3CA and ESR1mutations. 5/9 (56%) were PIK3CA-positive, and 4/9 (44%) were ESR1-positive. The median FES PET SUV was 6.47 in the PIK3CA-positive and 3.20 in the PIK3CA-negative subgroup (p 0.015). The median FES PET SUV was 4.30 in the ESR1-positive and 3.30 in the ESR1-negative subgroup (p = 0.794). Strong correlation was found between FES PET SUV and mutation count, approaching statistical significance (r = 0.94, p = 0.06). Conclusions: Our preliminary analysis demonstrates higher FES PET SUV in patients with PIK3CA and ESR1 mutations, as well as a trend for greater SUV in patients with a greater number of mutations, noting limitations of small sample size. Integrating brain FES PET with liquid biopsy has the potential to optimize treatment response in patients with ER-positive BCBM. This multi-modal approach may enhance our understanding of therapy resistance mechanisms by integrating biologically targeted PET with molecular profiling to guide treatment decisions in patients with ER+ BC BM. References 1. Barnholtz-Sloan JS, Sloan AE, Davis FG, et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004;22:2865-2872. 2. Lother D, Robert M, Elwood E, et al. Imaging in metastatic breast cancer, CT, PET/CT, MRI, WB-DWI, CCA: review and new perspectives. Cancer Imaging2023;23:53 Citation Format: A. Sharbatdaran, L. Pontolillo, E. Elmoujarkach, S. Nehmeh, A. Brandmaier, R. S. Magge, R. Ramakrishna, S. C. Pannullo, J. P. S. Knisely, K. F. P. Beal, J. R. Osborne, M. Cristofanilli, J. Ivanidze. Brain fes pet standardized uptake value association with esr1 and pik3ca genomic alterations [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 PS1-12-01.