Validation of a Radiosensitivity Molecular Signature in Breast Cancer

SA Eschrich, WJ Fulp, Y Pawitan, John Foekens, Marcel Smid, John Martens, M Echevarria, V Kamath, JH v.d. Lee, EE Harris, J van den Bergh, JF Torres-Roca

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Purpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients. Experimental Design: RSI was tested in 2 previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n = 159) and Erasmus Medical Center (n = 344). RSI was applied as previously described. Results: We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5-year relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, P = 0.0212), but there was no difference between RS/RR patients treated without RT (71% vs. 77%, P 0.6744), consistent with RSI being RT-specific (interaction term RSI x RT, P = 0.05). Similarly, in the Erasmus dataset, RT-treated RS patients had an improved 5-year distant metastasis-fre Conclusions: RSI is validated in 2 independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in 5 independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology. Clin Cancer Res; 18(18); 5134-43. (c) 2012 AACR.
Original languageUndefined/Unknown
Pages (from-to)5134-5143
Number of pages10
JournalClinical Cancer Research
Issue number18
Publication statusPublished - 2012

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  • EMC MM-03-86-01

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