ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer

Importance There are insufficient data comparing 16α- 18 F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence. Objective To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence. Design, Setting, and Participants This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024. Exposure Participants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm. Main Outcomes and Measures The outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences. Results A total of 124 patients were accrued, with 62 in cohort 1 (median IQR age, 52 32-84 years) and 62 in cohort 2 (median IQR age, 66 30-93 years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 ( P gt; .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 ( P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 ( P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT ( P = .13). Conclusions and Relevance In this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.