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

Abstract

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 (18 F-FES) noninvasively characterizes ER ligand-binding function of breast cancer lesions. Concordance of imaging and tissue assays should be established for 18 F-FES PET to be an alternative or complement to tissue biopsy for metastatic lesions. We conducted a metaanalysis of published results comparing 18 F-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 18 F-FES PET is useful for characterization of ER status of metastatic breast cancer lesions. We also review current best practices for conducting 18 F-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.

[18F]FDG and [18F]FES positron emission tomography for disease monitoring and assessment of anti-hormonal treatment eligibility in granulosa cell tumors of the ovary

“…Previous studies showed that FES uptake corresponds with ER expression on immunohistochemistry in breast cancer and uterine cancer [ 22 , 23 ]. Compared to immunohistochemical staining, FES-PET has a sensitivity of 0.81 and specificity of 0.86 in breast carcinoma studies [ 24 ]. We could not confirm this correlation in AGCTs, potentially due to the small sample size of the study, the time interval between tissue withdrawal and the FES-PET/CT, and varying ER expression levels between tumor lesions.…”

Menstrual Cycle Variations in Gray Matter Volume, White Matter Volume and Functional Connectivity: Critical Impact on Parietal Lobe

“…Furthermore, sex hormone binding globulin local concentrations keep readily releasable pools of steroids available and difficult to measure ( Södergård and Bäckström, 1987 ). However, it is clear that there is a relationship between blood serum and cerebral spinal fluid concentrations of neuroactive steroids and steroids in blood circulation clearly cross the blood brain barrier in both humans and animal models as demonstrated by 16a-18F-Fluoro-17b-Estradiol positron emission tomography ( Khayum et al, 2014 ; Kurland et al, 2020 ). Furthermore, blood serum progesterone and estradiol correlations with human cerebrospinal fluid are relatively rare with one notable study finding positive correlations of 0.731 for estradiol and 0.913 for progesterone ( Bäckström et al, 1976 ).…”

How Researchers, Clinicians and Patient Advocates Can Accelerate Lobular Breast Cancer Research

“…Lobular breast cancers have long been known to be more occult on imaging in the primary and metastatic setting. Progress has been made with [18F]-fluoro-estradiol (FES) positron-emission tomography (PET) imaging [23,24] and Fluciclovine (18F-FACBC) PET [25] and additional trials are ongoing, including one focused on FES-PET/CT Imaging of ILC (NCT04252859, https://clinicaltrials.gov/ct2/show/NCT04252859, accessed on 6 May 2021).…”