Prospective Pilot Study of 18 F-Fluoroestradiol PET/CT in Patients With Invasive Lobular Carcinomas.

Please see the Editorial Comment by Courtney Lawhn-Heath discussing this article. Please see the Author Interview associated with this article. Background: PET/CT using 18F-fluoroestradiol (FES) (FDA-approved in 2020) reveals tissues expressing estrogen receptors (ER). Invasive lobular carcinoma (ILC) is commonly ER-positive. Objective: This study's primary aim was to assess the frequency with which sites of histologically proven ILC show abnormal uptake on FES PET/CT. Methods: This prospective single-center pilot study, conducted from December 2020 to August 2021, enrolled patients with histologically confirmed ILC to undergo FES PET/CT; patients optionally underwent FDG PET/CT. Two nuclear radiologists assessed FES PET/CT and FDG PET/CT for abnormal uptake corresponding with known ILC sites at enrollment and for additional sites of abnormal uptake, resolving differences by consensus. The primary endpoint was the percentage of known ILC sites showing abnormal FES uptake. The alternative to the null hypothesis was that greater than 60% of sites would show abnormal FES uptake, exceeding the percentage of ILC showing abnormal FDG uptake in prior literature. A sample size of 24 biopsied lesions was pre-selected to provide 81% power for the alternative hypothesis (one-sided alpha, 0.10). Findings on FES PET/CT and FDG PET/CT were summarized for additional secondary endpoints. Results: The final analysis included 17 patients (mean age, 59.1±13.2 years) with 25 sites of histologically confirmed ILC at enrollment (22 breast lesions, two axillary lymph nodes, one distant metastasis). FES PET/CT showed abnormal uptake in 22/25 (88%) lesions, sufficient to reject the null hypothesis (p=.002). Thirteen patients underwent FDG PET/CT. Of sites of histologically confirmed ILC including additional sites detected and confirmed after enrollment, 4/23 (17%) were identified by only FES PET/CT, and 1/23 (4%) was identified by only FDG PET/ CT (p=.18). FES PET/CT identified additional lesions not detected by standard-of-care evaluation in 4/17 (24%) patients (two contralateral breast cancers and two metastatic axillary lymph nodes, all with subsequent histologic confirmation). FES PET/CT changed clinical stage with respect to standard-of-care evaluation in 3/17 (18%) patients. Conclusion: The trial's primary endpoint was met, showing the frequency of abnormal FES uptake among sites of histologically known ILC to be significantly greater than 60%. Clinical Impact: This pilot study demonstrates a potential role for FES PET/CT in evaluation of patients with ILC.