Genomic alterations and radioresistance in breast cancer: an analysis of the ProfiLER protocol.
Ann Oncol
; 28(11): 2773-2779, 2017 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-28945826
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tolerância a Radiação
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Neoplasias da Mama
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Rearranjo Gênico
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Biomarcadores Tumorais
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Carcinoma Lobular
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Carcinoma Ductal de Mama
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Recidiva Local de Neoplasia
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Ann Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2017
Tipo de documento:
Article