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Title: Intact Mre11/Rad50/Nbs1 Complex Predicts Good Response to Radiotherapy in Early Breast Cancer

Abstract

Purpose: 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 and Materials: 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 effectmore » of radiotherapy in patients with early breast cancer.« less

Authors:
 [1];  [2];  [3];  [4];  [2];  [2]
  1. Department of Biomedicine and Surgery, Division of Oncology, Linkoeping University, Linkoeping (Sweden). E-mail: karin.soderlund@ibk.liu.se
  2. Department of Biomedicine and Surgery, Division of Oncology, Linkoeping University, Linkoeping (Sweden)
  3. Department of Pathology and Cytology, Karolinska University Hospital, Stockholm (Sweden)
  4. Department of Medicine/Huddinge, Karolinska Institute, Stockholm (Sweden)
Publication Date:
OSTI Identifier:
20951614
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.12.005; PII: S0360-3016(06)03640-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; CHEMOTHERAPY; DNA REPAIR; ESTROGENS; MAMMARY GLANDS; PATIENTS; RADIOTHERAPY; RECEPTORS; TUMOR CELLS

Citation Formats

Soederlund, Karin, Stal, Olle, Skoog, Lambert, Rutqvist, Lars Erik, Nordenskjoeld, Bo, and Askmalm, Marie Stenmark. Intact Mre11/Rad50/Nbs1 Complex Predicts Good Response to Radiotherapy in Early Breast Cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.005.
Soederlund, Karin, Stal, Olle, Skoog, Lambert, Rutqvist, Lars Erik, Nordenskjoeld, Bo, & Askmalm, Marie Stenmark. Intact Mre11/Rad50/Nbs1 Complex Predicts Good Response to Radiotherapy in Early Breast Cancer. United States. doi:10.1016/j.ijrobp.2006.12.005.
Soederlund, Karin, Stal, Olle, Skoog, Lambert, Rutqvist, Lars Erik, Nordenskjoeld, Bo, and Askmalm, Marie Stenmark. Tue . "Intact Mre11/Rad50/Nbs1 Complex Predicts Good Response to Radiotherapy in Early Breast Cancer". United States. doi:10.1016/j.ijrobp.2006.12.005.
@article{osti_20951614,
title = {Intact Mre11/Rad50/Nbs1 Complex Predicts Good Response to Radiotherapy in Early Breast Cancer},
author = {Soederlund, Karin and Stal, Olle and Skoog, Lambert and Rutqvist, Lars Erik and Nordenskjoeld, Bo and Askmalm, Marie Stenmark},
abstractNote = {Purpose: 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 and Materials: 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.},
doi = {10.1016/j.ijrobp.2006.12.005},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 68,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
}