A Prospective Clinical Trial of 18F-Fluorestradiol (FES) PET/CT Compared to Standard of Care Imaging in Patients with Newly Diagnosed and Suspected Recurrent Breast Cancer

Introduction: Breast cancer metastases may be suboptimally detected by current standard-of-care imaging, which limits optimal treatment selection. 18F-Fluorestradiol (FES) is an Estrogen Receptor (ER)-targeting PET tracer, FDA-approved as an adjunct to biopsy for metastatic breast cancer. The value of FES for initial staging of locally advanced breast cancer and for detection of breast cancer recurrence following treatment is unknown. This ongoing prospective clinical trial is investigating the ability of FES PET/CT to detect disease in patients with locally advanced and suspected recurrent disease, compared against current standard-of-care imaging methods, using image guided biopsy to provide pathology as the gold standard for documenting the presence or absence of malignancy.

Methods: This IRB-approved prospective clinical trial (NCT04883814) is powered to evaluate 124 patients with ER+ breast cancer, 62 patients in each of 2 cohorts (Cohort 1: Locally advanced stage 2B-3C breast cancer and Cohort 2: Treated breast cancer with suspected recurrent disease.) Patients undergo both FES PET/CT and standard-of-care imaging (either CT/bone scan or FDG PET/CT). Lesions suspicious for distant metastases (cohort 1) or disease recurrence (cohort 2) undergo biopsy for tissue confirmation.

Results: To date, 39 subjects have been enrolled (21 in cohort 1; 18 in cohort 2). In cohort 1, FES detected biopsy proven distant metastases in 5/21 (24%), while standard-of-care imaging only detected 3 of these 5 patients with distant metastases. Thus, an additional 2/21 (10%) of patients had biopsy-proven distant metastases detected by FES PET/CT compared to disease detected on standard-of-care imaging. Additionally, 2/21 (10%) of patients also had pathologically proven axillary nodal metastases that were detected on FES PET/CT, but not detected on prior axillary ultrasound. In cohort 2, FES PET/CT detected sites of biopsy-proven recurrence in 7/18 (39%), while standard-of-care imaging only detected 4 of these 7 patients with distant recurrence. Thus, an additional 3/18 (17%) of patients had biopsy-proven sites of disease recurrence detected by FES PET/CT. Of note, FES PET/CT and standard-of-care imaging were positive in one patient each with benign subsequent biopsies, suggesting false positive imaging. An example of a subject from cohort 2 with a biopsy-proven benign FDG-avid lung lesion, yet biopsy-proven FES-avid multi-organ disease recurrence is shown in the figure.

Conclusions: This on-going prospective clinical trial provides preliminary evidence that FES PET/CT may outperform current standard-of-care imaging methods (CT/bone scan and FDG PET/CT) for the detection of clinically significant and treatment-altering disease in patients with ER+ breast cancer and either presumed locally advanced disease (cohort 1) or suspected disease recurrence following treatment (cohort 2). These two cohorts represent novel patient populations that may benefit from FES PET.

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