Abstract PO2-07-07: The role of PET imaging with 18F16α-fluoro-17β-fluoroestradiol in predicting response to endocrine therapies in patients with breast cancer

Abstract Background Fluoroestradiol F18 is a radioactive diagnostic agent (18F-FES) used with positron emission tomography (PET) imaging to detect estrogen-receptor (ER)-positive lesions in patients with breast cancer. Convened by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an expert working group published appropriate use criteria (AUC) for 18F-FES PET including, but not limited to, use of 18F-FES for selection of endocrine therapies. Quantitative determination of ER status, and thus treatment response, has the potential to prevent ineffective courses of endocrine therapies and associated therapeutic/financial burden. This meta-analysis reviewed the AUC-cited studies to assess the utility of 18F-FES in predicting treatment response to endocrine therapies. Methods Eight studies cited in the AUC were selected based on having comparable 18F-FES PET standardized uptake values (SUV) and progression-free survival (PFS) measures, and one additional study was included upon further systematic search of the same selected parameters defined in the AUC. With the nine studies (n = 327), we conducted three investigations to explore the association between: (1) the patient baseline 18F-FES PET SUVmean, across all lesions or across up to seven of the most intense lesions, and patient response to endocrine therapy (response/no response); (2) in the same population as investigation 1, the change (%) in 18F-FES PET SUV from baseline to at 7 to 10 days post-treatment; (3) the 18F-FES interlesional heterogeneity and PFS (months). Interlesional heterogeneity was qualitatively defined as patients displaying both 18F-FES positive and negative lesions versus those with all FES-positive lesions. Results A fixed effects model was used to analyze three studies (n = 102). Findings reveal that patients who responded to endocrine therapy had a significantly higher baseline SUVmean versus non-responders (mean difference 0.91; CI 95% 0.49 to 1.34; P 0.001); a sensitivity analysis was conducted via random effects modelling and revealed similar results (mean difference 0.92; CI 95% 0.48 to 1.36; P 0.001). This was consistent with findings from an additional analysis performed on two papers (n = 62), whereby odds ratio estimates indicated that a response to therapy is 89% less likely to occur when baseline 18F-FES SUVmax is 1.5 (OR 0.11; CI 95% 0.02 to 0.72 P = 0.02). Findings from the analysis of mean percentage change in 18F-FES SUV from baseline to 7-10 days post-treatment initiation showed no significant difference in the percentage change of SUV observed between responders and non-responders (mean difference -0.22; 95% CI -0.69 to 0.26; P = 0.37). The final heterogeneity analysis revealed higher median PFS in all FES-positive cohort, suggesting that this group may respond better to endocrine therapy (Table 1). Conclusion The AUC states that the presence of ER by immunohistochemistry may not be the optimal predictive biomarker for the success of endocrine therapies. Our findings support this statement, as a significantly higher baseline SUVmean of 18F-FES may serve as a predictive biomarker for endocrine therapy response. Patients with a 18F-FES lesion SUVmax 1.5 are 89% less likely to respond to endocrine therapies; patients demonstrating heterogeneity (FES+/FES- lesions) have a lower median PFS, reinforcing the predictive value of 18F-FES. Table 1. Median PFS scores from FES heterogeneity analysis *Patients with all FES positive lesions were categorised by the median ratio of FES/FDG SUVmax into low FES/FDG ( 0.96), and high FES/FDG (0.96); only patients with FES/FDG of 0.96 were included in the positive lesions arm. Citation Format: Nicholas DiGregorio, Christine Brand, Dustin Dunham, Eleanor McManus. The role of PET imaging with 18F16α-fluoro-17β-fluoroestradiol in predicting response to endocrine therapies in patients with breast cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-07-07.