Kayla Switalla, Natsuko Onishi, Ella F. Jones, Courtney Lawhn-Heath, Kimberly M. Ray, Deep Hathi, Julia C. Carmona-Bozo, Pouya Metanat, Alexandra J. Lopes, Israel Falade, Astrid Quirarte, Soumya Gottipati, Ruby Guo, Julissa Molina-Vega, Kami Pullakhandam, Teffany Joy Bareng, Margarita Watkins, A. Jo Chien, Bonnie N. Joe, Laura J. Esserman, Nola Hylton, Rita A. Mukhtar
PURPOSE: Invasive lobular carcinoma (ILC) of the breast presents challenges in monitoring response to neoadjuvant endocrine therapy (NET). Dedicated breast positron emission tomography with 18F-fluoroestradiol (FES-dbPET), a molecular imaging technique targeting the estrogen receptor (ER), may offer insight into treatment response. This study evaluated whether changes in FES-dbPET uptake before and after NET in patients with ILC correlate with treatment response indicators, and whether these associations differ by endocrine therapy type. METHODS: This prospective pilot study included patients with stage I-III ER positive, human epidermal growth factor 2 (HER2) negative ILC undergoing NET between 2017 and 2021. FES-dbPET was performed pre- and post-NET. Patients were stratified by type of NET received – aromatase inhibitor (AI) therapy or selective estrogen receptor modulator/degrader (SERM/SERD) therapy. The primary goal was to assess correlation between FES-dbPET parameters and change in tumor Ki-67 staining (%), a validated prognostic endpoint after NET. RESULTS: We enrolled 19 patients with ER + HER2- ILC, of whom 12 underwent both pre- and post-NET FES-dbPET. Among the AI cohort, changes in SUVpk and SULpk from pre- to post-NET each positively correlated with changes in Ki-67, though these associations did not reach statistical significance (r = 0.74, p = 0.256; and r = 0.75, p = 0.254, respectively). Conversely, among the SERM/SERD cohort, changes in SUVpk and SULpk strongly and positively correlated with changes in Ki-67 (r = 0.92, p = 0.027; and r = 0.92, p = 0.028, respectively). CONCLUSION: In this pilot study of 19 ER + ILC patients, change in FES uptake on dbPET showed some correlations with tumor response to NET. These findings suggest potential for FES-dbPET to capture tumor biology beyond that of standard imaging tools in predicting therapy response for patients with ILC. Further research with larger samples is needed to refine the role of FES-dbPET in improving neoadjuvant treatment monitoring and surgical planning in ILC patients.