18F-Fluoroestradiol Positron Emission Tomography in Breast Cancer Patients: Systematic Review of the Literature & Meta-Analysis

Purpose: The aim of the study was to determine the correlation between 16α-18F-fluoro- 17β-estradiol (18F-FES) uptake and the expression and functionality of estrogen receptors (ERs), as well as to evaluate the ability of 18F-FES PET to predict the response to hormonal therapy (HT) in patients with locally advanced or metastatic breast cancer (BC). Methods: Literature searches in the major literature databases were carried out in order to select English-language articles dealing with 18F-FES PET and BC. Studies that included patients with BC undergoing 18F-FES PET alone or in combination with other imaging modalities and included the absolute numbers of true-positive, true-negative, false-positive and false-negative test results were selected. Results: We found 23 journal articles, published between 1988 and December 2014, that critically evaluated the role of 18F-FES PET in BC patients. Two separate meta-analyses were carried out: 1- to assess the correlation between 18F-FES uptake and ER expression and 2- to determine the predictive value of 18F-FES in response to HT. For the first, we considered nine selected studies with a total of 238 patients. A pooled sensitivity of 82% (95% CI: 74-88%) and a pooled specificity of 95% (95% CI: 86-99%) for the evaluation of ER functional status by 18F-FES PET were found. Seven studies, with a total of 226 patients, were considered eligible for the analysis of prediction for response. The pooled sensitivities and specificities were 63.9% (95% CI: 46.2-79.2%) vs. 66.7% (95% CI: 52.1-79.2%), and 28.6% (95% CI: 17.3-42.2%) vs. 62.1% (95% CI: 48.4-74.5%), for a SUV cutoff of 1.5 and 2.0, respectively. Conclusion: A good correlation between 18F-FES uptake and ER expression by immunohistochemistry emerges, while the role of 18F-FES in predicting the response to endocrine therapy in advanced BC remains undetermined. Keywords: Breast cancer, estrogen receptor, fluoro-estradiol PET, endocrine therapy, response to treatment.