Estrogen Receptor Binding (18F-FES PET) and Glycolytic Activity (18F-FDG PET) Predict Progression-Free Survival on Endocrine Therapy in Patients with ER+ Breast Cancer

Purpose:¹⁸F-fluoroestradiol (FES) PET scans measure regional estrogen binding, and ¹⁸F-fluorodeoxyglucose (FDG) PET measures tumor glycolytic activity. We examined quantitative and qualitative imaging biomarkers of progression-free survival (PFS) in breast cancer patients receiving endocrine therapy.

Experimental Design: Ninety patients with breast cancer from an estrogen receptor–positive (ER⁺), HER2^– primary tumor underwent FES PET and FDG PET scans prior to endocrine therapy (63% aromatase inhibitor, 22% aromatase inhibitor and fulvestrant, 15% other). Eighty-four had evaluable data for PFS prediction.

Results: Recursive partitioning with 5-fold internal cross-validation used both FES PET and FDG PET measures to classify patients into three distinct response groups. FDG PET identified 24 patients (29%) with low FDG uptake, suggesting indolent tumors. These patients had a median PFS of 26.1 months (95% confidence interval, 11.2–49.7). Of patients with more FDG-avid tumors, 50 (59%) had high average FES uptake, and 10 (12%) had low average FES uptake. These groups had median PFS of 7.9 (5.6–11.8) and 3.3 months (1.4–not evaluable), respectively. Patient and tumor features did not replace or improve the PET measures' prediction of PFS. Prespecified endocrine resistance classifiers identified in smaller cohorts did not individually predict PFS.

Conclusions: A wide range of therapy regimens are available for treatment of ER⁺ metastatic breast cancer, but no guidelines are established for sequencing these therapies. FDG PET and FES PET may help guide the timing of endocrine therapy and selection of targeted and/or cytotoxic chemotherapy. A multicenter trial is ongoing for external validation. Clin Cancer Res; 23(2); 407–15. ©2016 AACR.

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