Fluoroestradiol (FES) and Fluorodeoxyglucose (FDG) PET Imaging in Patients with ER+, HER2-positive or HER2-negative Metastatic Breast Cancer

Background: F-Fluorodeoxyglucose (FDG) and F-Fluorestradiol (FES) have been FDA approved for measuring tumor glycolytic activity and estrogen receptor (ER) uptake, respectively, in clinical positron emission tomography (PET) imaging for patients with hormone-receptor (HR) positive metastatic breast cancer (MBC), but little is known about its utility in patients with breast tumors that overexpress human epidermal growth factor 2 (HER2). We hypothesize that comparing patterns of FDG and FES uptake in patients with HER2-positive versus HER2-negative MBC can guide further biologic and clinical studies into the HR/HER2-positive phenotype.

Methods: We conducted a retrospective study examining uptake in matched lesions for FES and FDG-PET scans, assessing these parameters in 213 patients with ER-positive/HER2-positive (n = 33) versus ER-positive/HER2-negative MBC (n = 180). We employed log-rank and t-tests to assess the association of HER2 status with outcome variables and the hypotheses that patients expressing HER2-positive disease lived longer than patient with HER2-negative disease.

Results: No difference in FES or FDG avidity was observed between patients with HER2-negative or HER2-positive tumor status. Limited data also suggests that patients with HER2-positive disease had better overall survival (p = 0.024), than those with HER2-negative disease, but not time-to-progression between the same patient cohorts.

Conclusion: This retrospective analysis suggests that there is a possible role for future trials using FES-PET in helping to select patients with ER+/HER2-positive primary tumors who retain ER expression at all sites of disease and may benefit from endocrine therapy.