Dna Repair Gene Expression Profile And Risk Of Locoregional Relapse In Locally Advanced Breast Cancer Patients

528 Background: The cytotoxicity of radiation therapy appears mainly mediated through the induction of DNA-double strand breaks. We explore whether DNA repair gene expression could be associated with the risk of locoregional recurrence (LRR) in locally advanced breast cancer patients. Methods: mRNA levels of 21 selected DNA repair genes were measured in tumors samples of 97 locally advanced breast cancer patients included in a phase III trial (CRH cohort), using quantitative reverse-transcriptase polymerase chain reaction. Normalized mRNA levels were evaluated for association with LRR-free survival (LRR-FS) and overall survival (OS). Results were validated in an independant cohort (Netherlands Cancer Institute: NKI cohort). Multivariate analysis, including known prognostic factors, was done to assess the association between gene expression profile of DNA repair genes and outcomes. Results: Overexpression of RAD51, PRKDC, and XRCC6 were associated with a higher risk of LRR in the CRH cohort. RAD51 was the only gene associated with LRR in the NKI cohort. With a median follow-up of 126 months (CRH cohort), the 5-year LRR-FS rates were 100% in patients (n = 61) with low RAD51, compared with 70% in patients (n = 36) with high RAD51 (p < 0.0001). The 5-year OS rates were 95% in patients with low RAD51, compared with 69% in patients with high RAD51 (p = 0.00026). RAD51 overexpression was associated with a higher risk of LRR (multiadjusted hazards ratio [HR], 12.83, 95% CI: 3.6 - 45.6) and a higher risk of death (multiadjusted hazards ratio [HR], 4.10, 95% CI: 1.7 - 9.7). RAD51 was also significantly associated with shorter LRR-FS and OS in the NKI cohort. Conclusions: Our results suggest that overexpression of RAD51, a key component of the homologous recombination and the DNA DSBs repair, is associated with a higher risk of LRR and death, and may be a prognostic marker of LRR in locally advanced breast cancer patients. No significant financial relationships to disclose.