Expression of the BRCA1 complex member BRE predicts disease free survival in breast cancer.
Breast cancer is one of the leading causes of cancer mortality in women. Recent advances in gene expression profiling have indicated that breast cancer is a heterogeneous disease and the current prognostication using clinico-pathological features is not sufficient to fully predict therapy response and disease outcome. In this retrospective study, we show that expression levels of BRE, which encodes a member of the BRCA1 DNA damage repair complex, predicted disease-free survival (DFS) in non-familial breast cancer patients. The predictive value of BRE expression depended on whether patients received radiotherapy as a part of their primary treatment. In radiotherapy-treated patients, high BRE expression predicted a favorable DFS (hazard ratio (HR) = 0.47, 95 % confidence interval (CI) = 0.28-0.78, p = 0.004), while in non-treated patients, high BRE expression predicted an adverse prognosis (HR = 2.59, 95 % CI = 1.00-6.75, p = 0.05). Among radiotherapy-treated patients, the prognostic impact of BRE expression was confined to patients with smaller tumors (HR = 0.23, 95 % CI = 0.068-0.75, p = 0.015) and it remained an independent factor after correction for the other prognostic factors age, tumor size, lymph node involvement, and histological grade (HR = 0.50, CI = 0.27-0.90, p = 0.021). In addition, high BRE expression predicted a favorable relapse-free survival in a publicly available dataset of 2,324 breast cancer patients (HR = 0.59, CI = 0.51-0.68, p < 0.001). These data indicate that BRE is an interesting candidate for future functional studies aimed at developing targeted therapies.
Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.
Sylvie M
SM
Noordermeer
Marloes
M
Wennemers
Saskia M
SM
Bergevoet
Adrian
A
van der Heijden
Evelyn
E
Tönnissen
Fred C G J
FC
Sweep
Joop H
JH
Jansen
Paul N
PN
Span
Bert A
BA
van der Reijden
D019313:BRCA1 Protein; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012189:Retrospective Studies
C091514:BABAM2 protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D009419:Nerve Tissue Proteins