Title: Early prediction of efficacy of endocrine therapy in breast cancer: pilot study and validation with 18F Fluoroestradiol (FES) PET/CT

Project Coordinator:
Alessandra GENNARI (Italy) E.O. Ospedali Galliera, Medical Oncology - Regione Liguria, Genoa

Project Partners:
Dino AMADORI (Italy) Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Bioscience Laboratory, Meldola (FC)
Etienne BRAIN (France) Institut Curie - Hôpital René Huguenin, Department of Medical Oncology, Saint-Cloud
Nadia HARBECK (Germany) University of Munich, Breast Center, Department of Obstetrics and Gynecology, Munich
Eva MUÑOZ-COUSELO (Spain) Vall d’Hebron Institute of Oncology (VHIO), Medical Oncology,Barcelona

Project Abstract:
Almost 70% of breast tumors are endocrine responsive, as defined by estrogen receptor (ER) expression by immunohistochemistry on the primary tumor, with a demonstrated predictive value on response to endocrine therapy. However it can be estimated that roughly 30% of ER positive breast cancer patients will re lapse despite adjuvant endocrine therapy. Moreover, it has also been shown that 10 to 20% of metastatic breast cancer lesions lose completely or partially the expression of hormone receptors. The early identification of those patients with ER positive breast cancer, not sensitive to endocrine therapy might help to improve systemic treatment options, sparing patients from unnecessary toxicities and inactive drugs. The availability [18F]fluoro-oestradiol-17β (18F-FES), an oestradiol analogue labeled with F18, may allow to test in vivo the performance of oestrogen receptors, by testing their linkage ability. In metastatic breast cancer,18F-FES uptake by metastatic lesions has been proposed to be a better predictor of response to endocrine therapy than ER expression itself. The aim of this proposal is to validate thepredictive value of18F-FES uptake at PET/CT scan in metastatic ER positive patients. The study will be developed as follows:
1. Clinical validation trial: this is a phase II randomized comparative clinical trial with a diagnostic agent (18F -FES), whose primary aim is to identify endocrine resistant patients.
2. Translational study: this will include the evaluation of estrogen-related genes on primary tumor and biopsies of metastatic sites. Expression data will then be correlated with 18F-FES uptake results.

(Project funded under JTC 2011)