Molecular imaging with 18F-fluoroestradiol (18F-FES) to assess intra-patient heterogeneity in metastatic breast cancer (MBC): A European TRANSCAN program

Abstract

Background: Endocrine responsiveness in Estrogen Receptor positive (ER+) MBC is based on the level of ER expression on the primary tumor and/or metastatic lesion. In this study, nested in the ET-FES JTC 2011 TRANSCAN project, we used molecular imaging with 18F-FES to explore intra-patient heterogeneity in ER expression at different metastatic sites and to identify patients who are not likely to benefit from ET. Methods: ER+patients at first relapse underwent at baseline a 18F-FES PET/CT plus a 18F-fluoro-2-deoxy-D-glucose (FDG) PET/CT. Patients were classified into 4 18F-FES/ FDG subgroups based on the proportion of FDG avid metastatic tumor load with high 18F-FES uptake (Gebhart Ann Oncol 2016). Subgroup A was considered positive (100% of concordance); subgroups B and C were considered partially positive or partially negative, with different degrees of 18F-FES uptake; subgroup D was considered negative (100% of discordance). Patients with global SUV ≥2 received first line ET while those with SUV <2 were randomized to ET or to chemotherapy. HR for progression was calculated comparing patients with concordant 18F-FES/FDG lesions (group A) with all the other patients. Results: So far, 80 patients have been enrolled in the ET-FES trial and 79 are included in the present analysis. At baseline evaluation, 53 patien4ts (67.1%) were classified as 18F-FDG/18F-FES positive (A); 16 patients (20.3%) showed some degree of intrapatient heterogeneity (11 group B and 5 group C); 10 patients (12.6%) were classified as D with all lesions being 18F-FES negative. In the 64 patients with a response evaluation available at time of analysis, 26 have shown progression. ET was administered in 40 patients in group A and in 24 patients in groups B + C +D. The use of ET alone in partially positive (B) or partially negative (C) or negative (D) patients was associated with a 79% absolute increase in the risk of progression (HR 1.79, p 0.2) compared to patients in group A. Conclusions: Pretreatment ER biomarker imaging at different metastatic sites with 18F-FES PET/CT indicate the presence of a significant intra-patient heterogeneity in MBC and represents a promising tool to select patients who are unlikely to benefit from ET alone. Clinical trial identification: EUDRACT 2013-000-287-29.