Clinical Validity of 16α-[18F]Fluoro-17β-Estradiol Positron Emission Tomography/Computed Tomography to Assess Estrogen Receptor Status in Newly Diagnosed Metastatic Breast Cancer

PURPOSE Determining the estrogen receptor (ER) status is essential in metastatic breast cancer (MBC) management. Whole-body ER imaging with 16α-[18F]fluoro-17β-estradiol positron emission tomography ([18F]FES-PET) is increasingly used for this purpose. To establish the clinical validity of the [18F]FES-PET, we studied the diagnostic accuracy of qualitative and quantitative [18F]FES-PET assessment to predict ER expression by immunohistochemistry in a metastasis. METHODS In a prospective multicenter trial, 200 patients with newly diagnosed MBC underwent extensive workup including molecular imaging. For this subanalysis, ER expression in the biopsied metastasis was related to qualitative whole-body [18F]FES-PET evaluation and quantitative [18F]FES uptake in the corresponding metastasis. A review and meta-analysis regarding [18F]FES-PET diagnostic performance were performed. RESULTS Whole-body [18F]FES-PET assessment predicted ER expression in the biopsied metastasis with good accuracy: a sensitivity of 95% (95% CI, 89 to 97), a specificity of 80% (66 to 89), a positive predictive value (PPV) of 93% (87 to 96), and a negative predictive value (NPV) of 85% (72 to 92) in 181 of 200 evaluable patients. Quantitative [18F]FES uptake predicted ER immunohistochemistry in the corresponding metastasis with a sensitivity/specificity of 91%/69% and a PPV/NPV of 90%/71% in 156 of 200 evaluable patients. For bone metastases, PPV/NPV was 92%/81%. Meta-analysis with addition of our data has increased diagnostic performance and narrowed the 95% CIs compared with previous studies with a sensitivity/specificity of both 86% (81 to 90 and 73 to 93, respectively). CONCLUSION In this largest prospective series so far, we established the clinical validity of [18F]FES-PET to determine tumor ER status in MBC. In view of the high diagnostic accuracy of qualitatively assessed whole-body [18F]FES-PET, this noninvasive imaging modality can be considered a valid alternative to a biopsy of a metastasis to determine ER status in newly MBC (ClinicalTrials.gov identifier: NCT01957332 ).