Breast cancer (BC) is a heterogeneous disease in which estrogen receptor (ER) expression plays an important role in most tumors. A clinical dilemma may arise when a metastasis biopsy to determine the ER status cannot be performed safely or when ER heterogeneity is suspected between tumor lesions. Whole-body ER imaging, such as 16a-18 F-fluoro-17b-estradiol ( 18 F-FES) PET, may have added value in these situations. However, the role of this imaging technique in routine clinical practice remains to be further determined. Therefore, we assessed whether the physician's remaining clinical dilemma after the standard workup was solved by the 18 F-FES PET scan. Methods: This retrospective study included 18 F-FES PET scans of patients who had (or were suspected to have) ER-positive metastatic BC and for whom a clinical dilemma remained after the standard workup. The scans were performed at the University Medical Center of Groningen between November 2009 and January 2019. We investigated whether the physician's clinical dilemma was solved, defined either as solving the clinical dilemma through the 18 F-FES PET results or as basing a treatment decision directly on the 18 F-FES PET results. In addition, the category of the clinical dilemma was reported, as well as the rate of 18 F-FES-positive or -negative PET scans, and any correlation to the frequency of solved dilemmas was determined. Results: One hundred 18 F-FES PET scans were performed on 83 patients. The clinical dilemma categories were inability to determine the extent of metastatic disease or suspected metastatic disease with the standard workup (n 5 52), unclear ER status of the tumor (n 5 31), and inability to determine which primary tumor caused the metastases (n 5 17). The dilemmas were solved by 18 F-FES PET in 87 of 100 scans (87%). In 81 of 87 scans, a treatment decision was based directly on 18 F-FES PET results (treatment change, 51 scans; continuance, 30 scans). The frequency of solved dilemmas was not related to the clinical dilemma category (P 5 0.334). However, the frequency of solved dilemmas was related to whether scans were 18 F-FES-positive (n 5 63) or 18 F-FES-negative (n 5 37; P , 0.001). Conclusion: For various indications, the 18 F-FES PET scan can help to solve most clinical dilemmas that may remain after the standard workup. Therefore, the 18 F-FES PET scan has added value in BC patients who present the physician with a clinical dilemma.

Background: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [18F]-FES uptake. We evaluated whether [18F]-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 [18F]-FES-PET, liver metastasis biopsy, CT-scan, and [18F]-FDG-PET. [18F]-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 [18F]-FES-PET if background correction and separate thresholds are applied.