Phase 2 trial of Estrogen Receptor (ER)-targeted Positron Emission Tomography (PET) for Initial Staging and Suspected Recurrence in Patients with ER+ breast cancer

Introduction: There is no data comparing 16α-18F-fluoro-17β-estradiol (FES) Positron Emission Tomography (PET) to current standard-of-care (SOC) imaging for staging locally advanced breast cancer or evaluating suspected recurrences. This trial was designed to determine the detection rate of FES PET/CT and SOC imaging for 1) distant metastases in patients with ER+ locally advanced BC and 2) recurrences in patients with ER+ BC and suspected recurrence.

Methods: A phase 2 trial (NCT04883814) was performed involving 124 subjects with ER+ breast cancer in 62 subjects with locally advanced disease (cohort 1) and 62 subjects with suspected recurrence (cohort 2). Subjects underwent both SOC imaging and FES PET/CT. Lesions suspicious on imaging were biopsied for a pathologic reference standard. Cohort sizes provided 80% power to detect an absolute difference of 20% in detection rates.

Results: Breast cancer histologies were no special type (n=92), invasive lobular carcinoma (ILC, n = 30), and other (n=2). SOC imaging was CT/bone scan (n=62) and FDG PET/CT (n=62). In cohort 1, SOC imaging detected 12/14 histologic true positives with 4 false positives, while FES detected 11/14 true positives and no false positives. In cohort 2, SOC detected 16/23 true positives with 2 false positives, while FES detected 18/23 true positives with 1 false positive. There was no significance difference between the performance of SOC and FES for the detection of true positive distant metastases (p > .99) or true positive recurrences (p = .77). In the 30 patients with ILC histology in both cohorts, SOC detected 5/11 true positives, while FES detected 9/11 (p = .29). There were 6 false positives on SOC imaging and 1 false positive on FES PET/CT (p = 0.13).

Conclusions: With pathology as the gold standard, no difference was found between FES PET/CT and current SOC imaging for the detection of 1) distant metastases in patients locally advanced breast cancer and 2) recurrences in patients with suspected recurrence. This data supports the use of FES PET/CT for both of these clinical indications. There was a strong signal that FES PET/CT may be superior to SOC in patients with ILC. A future trial of only patients with ILC is warranted.

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