Abstract A54: Met and its ligand HGF predict radiotherapy response in premenopausal breast cancer patients

Post-operative radiotherapy effectively decreases the risk for loco-regional recurrence in breast cancer. However, some patients display signs of radioresistance. There are few biomarkers used in the clinic today to predict response to radiotherapy, and patients continue to receive unnecessary treatment. Studies propose a role for the receptor tyrosine kinase Met and its ligand HGF in radioresistance. Therefore, it was aimed in this study to determine MET and HGF copy numbers, Met and HGF expression, and phosphorylated Met expression in breast cancers to elucidate Met and HGF9s role in radiotherapy response. MET and HGF copy numbers were determined by digital droplet PCR in 205 pre-menopausal patients, randomized to receive either radio- or chemotherapy. Immunohistochemical staining of Met, phosphorylated Met, and HGF could be performed on 228 tumor tissue samples in this cohort. Increased MET and HGF copy numbers, more than two copies, were detected in 33% and 21% of the tumors, respectively. MET and HGF amplification, more than three copies, was detected in 8% and 7% of the tumors, respectively. Interestingly, patients with tumours with MET amplification tended to relapse at a higher rate than patients without amplification. This was more prominent in patients with triple-negative breast cancer, where both MET amplification and increased copy number were correlated with a shorter recurrence-free survival. High stromal HGF expression, but not HGF copy number, was also shown to be correlated with shorter survival. Both high cytoplasmic phosphorylated Met and high cytoplasmic HGF predicted better response to radiotherapy, compared with low expression. Similar results were seen for MET and HGF increased copy number. A tendency of opposite results were obtained with total membranous Met and stromal HGF. Patients with tumors expressing low levels of these proteins had more benefit from radiotherapy. This suggests that MET and HGF copy gain is not enough for a favorable radiotherapy response, the status of the resulting proteins is additionally of importance. Citation Format: Cynthia Veenstra, Gizeh Perez-Tenorio, Bo Nordenskoljd, Tommy Fornander, Olle Stal. Met and its ligand HGF predict radiotherapy response in premenopausal breast cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A54.