Analyzing the Estrogen Receptor Status of Liver Metastases with [(18)F]-FES-PET in Patients with Breast Cancer

Background: Positron emission tomography (PET) with 16α-[(18)F]-fluoro-17β-estradiol ([(18)F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [(18)F]-FES uptake. We evaluated whether [(18)F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard. Methods: Patients with metastatic breast cancer (n = 23) were included if they had undergone a [(18)F]-FES-PET, liver metastasis biopsy, CT-scan, and [(18)F]-FDG-PET. [(18)F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined. Results: Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER− metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive. Conclusion: In the majority of liver metastases, ER status can be determined with [(18)F]-FES-PET if background correction and separate thresholds are applied.