Whole‐Body Characterization of Estrogen Receptor Status in Metastatic Breast Cancer with 16α‐18F‐Fluoro‐17β‐Estradiol Positron Emission Tomography: Meta‐Analysis and Recommendations for Integration into Clinical Applications

Estrogen receptor (ER) status by immunohistochemistry (IHC) of cancer tissue is currently used to direct endocrine therapy in breast cancer. Positron emission tomography (PET) with 16α‐18F‐fluoro‐17β‐estradiol (18F‐FES) noninvasively characterizes ER ligand–binding function of breast cancer lesions. Concordance of imaging and tissue assays should be established for 18F‐FES PET to be an alternative or complement to tissue biopsy for metastatic lesions. We conducted a meta‐analysis of published results comparing 18F‐FES PET and tissue assays of ER status in patients with breast cancer. PubMed and EMBASE were searched for English‐language manuscripts with at least 10 patients and low overall risk of bias. Thresholds for imaging and tissue classification could differ between studies but had to be clearly stated. We used hierarchical summary receiver‐operating characteristic curve models for the meta‐analysis. The primary analysis included 113 nonbreast lesions from 4 studies; an expanded analysis included 327 total lesions from 11 studies. Treating IHC results as the reference standard, sensitivity was 0.78 (95% confidence region 0.65–0.88) and specificity 0.98 (0.65–1.00) for the primary analysis of nonbreast lesions. In the expanded analysis including non‐IHC tissue assays and all lesion sites, sensitivity was 0.81 (0.73–0.87) and specificity 0.86 (0.68–0.94). These results suggest that 18F‐FES PET is useful for characterization of ER status of metastatic breast cancer lesions. We also review current best practices for conducting 18F‐FES PET scans. This imaging assay has potential to improve clinically relevant outcomes for patients with (historically) ER‐positive metastatic breast cancer, including those with brain metastases and/or lobular histology. Implications for Practice 16α‐18F‐fluoro‐17β‐estradiol positron emission tomography (18F‐FES PET) imaging assesses estrogen receptor status in breast cancer in vivo. This work reviews the sensitivity and specificity of 18F‐FES PET in a meta‐analysis with reference tissue assays and discusses best practices for use of the tracer as an imaging biomarker. 18F‐FES PET could enhance breast cancer diagnosis and staging as well as aid in therapy selection for patients with metastatic disease. Tissue sampling limitations, intrapatient heterogeneity, and temporal changes in molecular markers make it likely that 18F‐FES PET will complement existing assays when clinically available in the near future. Positron emission t