Research article
Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy
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* Corresponding author: Mårten Fernö Marten.Ferno@med.lu.se
1 Institute of Clinical Sciences, Department of Oncology, University Hospital, SE 221 85 Lund, Sweden
2 Computational Biology and Biological Physics, Department of Theoretical Physics, Lund University, SE 223 68 Lund, Sweden
3 Department of Surgery, Karolinska University Hospital in Solna, SE 171 76 Stockholm, Sweden
4 Department of Oncology, Sahlgrenska University Hospital, SE 413 45 Gothenburg, Sweden
5 Department of Clinical and Experimental Medicine, Division of Oncology, Linköping University, University Hospital, SE 581 85 Linköping, Sweden
6 Department of Pathology, Halmstad Hospital, SE 302 33 Halmstad, Sweden
Breast Cancer Research 2008, 10:R34 doi:10.1186/bcr1997
Published: 22 April 2008Abstract
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.