18F-Fluoroestradiol PET/CT for Predicting Benefit from Endocrine Therapy in Patients with Estrogen Receptor–Positive Breast Cancer: A Systematic Review and Metaanalysis

¹⁸F-fluoroestradiol (¹⁸F-FES) PET/CT has been investigated as a potential biomarker to predict response to endocrine therapies in patients with estrogen receptor (ER)–positive breast cancer. Although previous findings were promising, most had limited statistical significance because of small individual sample sizes. Therefore, we performed a systematic review and metaanalysis of the ¹⁸F-FES PET/CT literature to increase our power to evaluate the utility of ¹⁸F-FES PET/CT as a biomarker for prediction of clinical benefit from endocrine therapy in patients with ER-positive breast cancer. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, MEDLINE via OVID, Embase, Web of Science, Emcare, and the Cochrane Central Register of Controlled Trials through November 1, 2024, for studies that included patients with ER-positive breast cancer who received an ¹⁸F-FES PET/CT at baseline and received subsequent endocrine therapy. For each eligible study, data were extracted using a predesigned data extraction form. Random effects models were used to estimate the likelihood of clinical benefit from endocrine therapy after a positive ¹⁸F-FES PET scan, the likelihood of clinical benefit from endocrine therapy after a negative ¹⁸F-FES PET scan, and the risk ratio of clinical benefit from endocrine therapy comparing those who were ¹⁸F-FES–positive to those who were ¹⁸F-FES–negative. Results: From 1,105 database records retrieved, 12 studies were included in the metaanalysis (n = 308 participants with data on ¹⁸F-FES PET results and response to endocrine therapy). The likelihood of clinical benefit after a positive ¹⁸F-FES PET scan was 66% (95% CI, 51%–79%; I² = 76.6%; n = 227 participants) and the likelihood after a negative ¹⁸F-FES PET scan was 11% (95% CI, 3.5%–22%; I² = 0.0%; n = 81 participants). The risk ratio of response that compared those who were ¹⁸F-FES–positive with those who were ¹⁸F-FES–negative was 3.21 (95% CI, 1.96–5.25; I² = 0.0%; P < 0.0001). Conclusion:¹⁸F-FES PET is a successful biomarker for predicting the likelihood of success of endocrine therapy in patients with ER-positive breast cancer. There is strong evidence that patients with ¹⁸F-FES–negative disease are unlikely to derive clinical benefit from endocrine therapies, despite the presence of ER-positive disease on pathology. This supports a role for ¹⁸F-FES PET in identifying patients for whom endocrine therapy may or may not be an appropriate treatment option.