ET-FES

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.

From a scientific and “networking” point of view, in the past months there has been an increased interest in molecular imaging through experimental radiotracers in oncology, particularly focused on breast cancer. In fact, with the approval and introduction into the clinical practice of effective but extremely expensive new targeted agents, the sustainability of the cost of these medications is rapidly becoming an emergency in health policies in the EU. For this reason, personalized medicine is quickly becoming an unmet need also in health economics. In this perspective, our group, initially merged in the ET-Fes Transcan project, gained new researchers from two of the major cancer institute in Europe, with outstanding experience in Molecular imaging and Experimental radiotracers, such as the Institute Jules Bordet in Brussels (Martine Piccart) and the Oncology center at Groeningen University (Elisabeth de Vries, Carolien Schroder).