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Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast conservation surgery with or without postoperative radiotherapy

Niméus, Emma LU ; Krogh, Morten LU ; Malmström, Per LU ; Forsare, Carina LU ; Fredriksson, I; Karlsson, P; Nordenskjöld, B; Stål, O; Östberg, G and Peterson, Carsten LU , et al. (2008) In Breast Cancer Research 10(2).
Abstract
Introduction



Some patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.

Methods



We performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.

Results



Within the... (More)
Introduction



Some patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.

Methods



We performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.

Results



Within the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-).

Conclusion



A highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research
volume
10
issue
2
publisher
BioMed Central
external identifiers
  • wos:000255941100022
  • scopus:48949119492
ISSN
1465-5411
DOI
10.1186/bcr1997
project
CREATE Health
language
English
LU publication?
yes
id
38578355-98dc-42ac-94f9-3bd000fe5fa1 (old id 818801)
date added to LUP
2008-01-03 09:16:21
date last changed
2017-10-22 03:50:41
@article{38578355-98dc-42ac-94f9-3bd000fe5fa1,
  abstract     = {Introduction<br/><br>
<br/><br>
Some patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.<br/><br>
Methods<br/><br>
<br/><br>
We performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.<br/><br>
Results<br/><br>
<br/><br>
Within the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-).<br/><br>
Conclusion<br/><br>
<br/><br>
A highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy.},
  author       = {Niméus, Emma and Krogh, Morten and Malmström, Per and Forsare, Carina and Fredriksson, I and Karlsson, P and Nordenskjöld, B and Stål, O and Östberg, G and Peterson, Carsten and Fernö, Mårten},
  issn         = {1465-5411},
  language     = {eng},
  number       = {2},
  publisher    = {BioMed Central},
  series       = {Breast Cancer Research},
  title        = {Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast conservation surgery with or without postoperative radiotherapy},
  url          = {http://dx.doi.org/10.1186/bcr1997},
  volume       = {10},
  year         = {2008},
}