Intact Mre11/Rad50/Nbs1 complex predicts good response to radiotherapy in early breast cancer.
OBJECTIVE
To investigate the expression and predictive role of the Mre11/Rad50/Nbs1 (MRN) complex and the ataxia-telangiectasia mutated protein (ATM) for the outcome of radiotherapy in breast cancer patients.


METHODS
The protein expression of ATM and the DNA repair proteins in the MRN complex were investigated using immunohistochemistry in tumors from 224 women with early breast cancer, who were randomized to receive postoperative radiotherapy or adjuvant chemotherapy.


RESULTS
Compared with normal breast tissue, the staining intensity of Mre11, Rad50, Nbs1, and ATM was reduced in a majority of the tumors. Weak expression of the MRN complex was correlated with high histologic grade and estrogen receptor negativity (p = 0.01 and p = 0.0001, respectively). Radiotherapy significantly reduced the risk of local recurrence as compared with chemotherapy (p = 0.04). The greatest benefit of radiotherapy was seen in patients with moderate/strong expression of the MRN complex (relative risk = 0.27, 95% confidence interval = 0.098-0.72, p = 0.009), whereas patients with negative/weak MRN expression had no benefit of radiotherapy compared with adjuvant chemotherapy. These results suggest that an intact MRN complex is important for the tumor cell eradicating effect of radiotherapy.


CONCLUSIONS
Reduced expression of the MRN complex predicts a poor effect of radiotherapy in patients with early breast cancer.
Söderlund
Karin
K
Department of Biomedicine and Surgery, Division of Oncology, Linköping University, Linköping, Sweden. karin.soderlund@ibk.liu.se
Stål
Olle
O
Skoog
Lambert
L
Rutqvist
Lars Erik
LE
Nordenskjöld
Bo
B
Askmalm
Marie Stenmark
MS
D017766:Acid Anhydride Hydrolases; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D000076228:MRE11 Homologue Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes