E Bernichon1, A Vallard2, Q Wang3, V Attignon3, D Pissaloux3, T Bachelot1, P E Heudel1, I Ray-Coquard1, E Bonnet1, A de la Fouchardière4, C Faure5, N Chopin5, F Beurrier5, S Racadot6, M P Sunyach6, C Rancoule2, D Perol7, V Corset7, V Agrapart7, F Tinquaut8, J-Y Blay9, N Magné10, O Trédan9. 1. Department of Medical Oncology. 2. Department of Radiation Oncology, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez. 3. Department of Translational Research. 4. Department of Pathobiology. 5. Department of Surgery. 6. Department of Radiation Oncology. 7. Department of Clinical Research, Léon Bérard Cancer Centre, Lyon. 8. Department of Hygée Center, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez. 9. Department of Translational Research; Department of Medical Oncology. 10. Department of Radiation Oncology, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez; Department of Laboratoire de Radiobiologie Cellulaire et Moléculaire, CNRS UMR 5822, Institut de Physique Nucléaire de Lyon, IPNL, Lyon Medicine University, Lyon, France. Electronic address: nicolas.magne@icloire.fr.
Abstract
BACKGROUND: Breast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, party related to a possible radiotherapy resistance leading to local-regional recurrences (LRR). The objective of the present study was to identify predictive molecular biomarkers of LRR of BC. PATIENTS AND METHODS: Genetic profile of 146 BC patients' tumours included in the ProfiLER clinical trial (NC01774409) between 2013 and 2016 were analysed using next-generation-sequencing and comparative-genomic-hybridization tests. Patients and tumour characteristics were retrospectively collected and analysed for association with genomic rearrangements (mutations, amplification, deletions). Only gene alterations observed in >3% of the tumours were selected. RESULTS: A total of 193 genomic rearrangements were identified, and 16 were observed in >3% of tumours. One was statistically correlated to the risk of local relapse. A median loco-regional progression-free survival (LRPFS) of 23.6 years was reported for PIK3CA mutation carriers (n = 31, 21.2%) versus 9.9 years for PIK3CA wild-type patients (HR 0.27, 95% CI 0.12-0.65, P = 0.002 in univariate analysis). PIK3CA mutation was identified as an independent protective factor on LRR using multivariate analysis (HR 0.29, 95% CI 0.09-0.99, P = 0.047). All other mutations, amplifications or deletions were not found associated with LRPFS. CONCLUSION: PIK3CA mutation was associated with a lower risk of local relapse in this population of BCs. This is consistent with recent studies suggesting PIK3CA to be part of biological pathways impacting the radiosensitivity.
BACKGROUND: Breast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, party related to a possible radiotherapy resistance leading to local-regional recurrences (LRR). The objective of the present study was to identify predictive molecular biomarkers of LRR of BC. PATIENTS AND METHODS: Genetic profile of 146 BC patients' tumours included in the ProfiLER clinical trial (NC01774409) between 2013 and 2016 were analysed using next-generation-sequencing and comparative-genomic-hybridization tests. Patients and tumour characteristics were retrospectively collected and analysed for association with genomic rearrangements (mutations, amplification, deletions). Only gene alterations observed in >3% of the tumours were selected. RESULTS: A total of 193 genomic rearrangements were identified, and 16 were observed in >3% of tumours. One was statistically correlated to the risk of local relapse. A median loco-regional progression-free survival (LRPFS) of 23.6 years was reported for PIK3CA mutation carriers (n = 31, 21.2%) versus 9.9 years for PIK3CA wild-type patients (HR 0.27, 95% CI 0.12-0.65, P = 0.002 in univariate analysis). PIK3CA mutation was identified as an independent protective factor on LRR using multivariate analysis (HR 0.29, 95% CI 0.09-0.99, P = 0.047). All other mutations, amplifications or deletions were not found associated with LRPFS. CONCLUSION: PIK3CA mutation was associated with a lower risk of local relapse in this population of BCs. This is consistent with recent studies suggesting PIK3CA to be part of biological pathways impacting the radiosensitivity.