Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer

Autor: Miljana Tanić, Ana Krivokuća, Milena Čavić, Jasmina Mladenović, Vesna Plesinac Karapandžić, Stephan Beck, Siniša Radulović, Snezana Susnjar, Radmila Janković
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Radiation Oncology, Vol 13, Iss 1, Pp 1-10 (2018)
Druh dokumentu: article
ISSN: 1748-717X
DOI: 10.1186/s13014-018-1129-4
Popis: Abstract Background Radiation therapy is an indispensable part of various treatment modalities for breast cancer. Specifically, for non-inflammatory locally advanced breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently indicated as a second line therapy in the event of lack of response to neoadjuvant chemotherapy. Still approximately one third of patients fails to respond favourably to pRT. The aim of this study was to explore molecular mechanisms underlying differential response to radiotherapy (RT) to identify predictive biomarkers and potential targets for increasing radiosensitivity. Methods The study was based on a cohort of 134 LABC patients, treated at the Institute of Oncology and Radiology of Serbia (IORS) with pRT, without previous or concomitant systemic therapy. Baseline transcriptional profiles were established using Agilent 60 K microarray platform in a subset of 23 formalin-fixed paraffin-embedded (FFPE) LABC tumour samples of which 11 radiotherapy naïve and 3 post-radiotherapy samples passed quality control and were used for downstream analysis. Biological networks and signalling pathways underlying differential response to RT were identified using Ingenuity Pathways Analysis software. Predictive value of candidate genes in the preoperative setting was further validated by qRT-PCR in an independent subset of 60 LABC samples of which 42 had sufficient quality for data analysis, and in postoperative setting using microarray data from 344 node-negative breast cancer patients (Erasmus cohort, GSE2034 and GSE5327) treated either with surgery only (20%) or surgery with RT (80%). Results We identified 192 significantly differentially expressed genes (FDR
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