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

Emma Niméus-Malmström¹ , Morten Krogh² , Per Malmström¹ , Carina Strand¹ , Irma Fredriksson³ , Per Karlsson⁴ , Bo Nordenskjöld⁵ , Olle Stål⁵ , Görel Östberg⁶ , Carsten Peterson² and Mårten Fernö¹

¹Institute of Clinical Sciences, Department of Oncology, University Hospital, SE 221 85 Lund, Sweden

²Computational Biology and Biological Physics, Department of Theoretical Physics, Lund University, SE 223 68 Lund, Sweden

³Department of Surgery, Karolinska University Hospital in Solna, SE 171 76 Stockholm, Sweden

⁴Department of Oncology, Sahlgrenska University Hospital, SE 413 45 Gothenburg, Sweden

⁵Department of Clinical and Experimental Medicine, Division of Oncology, Linköping University, University Hospital, SE 581 85 Linköping, Sweden

⁶Department of Pathology, Halmstad Hospital, SE 302 33 Halmstad, Sweden

author email corresponding author email

Breast Cancer Research 2008, 10:R34doi:10.1186/bcr1997


Published:	22 April 2008

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 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.