DNA Repair Gene Expression and Risk of Locoregional Relapse in Breast Cancer Patients

Journal Article · Fri Oct 01 00:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.07.1735· OSTI ID:21436170

Cizeron-Clairac, Geraldine ^[1]

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1. INSERM U735, Centre Rene Huguenin, Saint Cloud (France)

Purpose: Radiation therapy appears to kill cells mainly by inducing DNA double-strand breaks. We investigated whether the DNA repair gene expression status might influence the risk of locoregional recurrence (LRR) in breast cancer patients. Methods and Materials: We used a quantitative reverse transcriptase PCR-based approach to measure messenger RNA levels of 20 selected DNA repair genes in tumor samples from 97 breast cancer patients enrolled in a phase III trial (Centre Rene Huguenin cohort). Normalized mRNA levels were tested for an association with LRR-free survival (LRR-FS) and overall survival (OS). The findings were validated in comparison with those of an independent cohort (Netherlands Cancer Institute (NKI) cohort). Multivariate analysis encompassing known prognostic factors was used to assess the association between DNA repair gene expression and patient outcome. Results: RAD51 was the only gene associated with LRR in both cohorts. With a median follow-up of 126 months in the CRH cohort, the 5-year LRR-FS and OS rates were 100% and 95% in the 61 patients with low RAD51 expression, compared with 70% and 69% in the 36 patients with high RAD51 expression, respectively (p < 0.001). RAD51 overexpression was associated with a higher risk of LRR (hazard ratio [HR], 12.83; 95% confidence interval [CI], 3.6-45.6) and death (HR, 4.10; 95% CI, 1.7-9.7). RAD51 overexpression was also significantly associated with shorter LRR-FS and OS in the NKI cohort. Conclusions: Overexpression of RAD51, a key component of the homologous DNA repair pathway, is associated with poor breast cancer outcome. This finding warrants prospective studies of RAD51 as a prognosticator and therapeutic target.

• OSTI ID: 21436170
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 78, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2009.07.1735; PII: S0360-3016(09)02965-4; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
DNA REPAIR
GENES
HEALTH HAZARDS
MAMMARY GLANDS
MESSENGER-RNA
NEOPLASMS
RADIOTHERAPY
STRAND BREAKS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
DISEASES
DNA DAMAGES
GLANDS
HAZARDS
MEDICINE
NUCLEAR MEDICINE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RADIOLOGY
REPAIR
RNA
THERAPY