Genomic alterations and radioresistance in breast cancer: an analysis of the ProfiLER protocol.

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 analyzed for association with genomic rearrangements (mutations, amplification, deletions). Only gene alterations observed in > 3% of the tumours were selected.Results: 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, CI95% (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, CI95% (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 radio-sensitivity.

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