Emma Niméus, Morten Krogh, Per Malmström, Carina Strand, Irma Fredriksson, Per Karlsson, Bo Nordenskjöld, Olle Stål, Görel Östberg, Carsten Peterson and Mårten Fernö
Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast conservation surgery, with or without postoperative radiotherapy
Breast Cancer Research 10, R34 (2008)

Background: Some patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, while 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 if gene-expression profiling would add further information.
Methods: We performed gene-expression analysis (oligo-nucleotide 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 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-characteristics (ROC) area was 0.91 and 5,237 of 26,824 reporters had a p-value below 0.001 (false discovery rate of 0.005). This gene-expression profile provides substantially added value to conventional clinical markers, e.g., age, histological grade, and tumor size in predicting local recurrence despite radiotherapy. Within the estrogen-receptor-negative subgroup, a weaker, but still significant, signal was found (ROC-area = 0.74). The ROC-area for distinguishing patients that develop local recurrence from those that remain local-recurrence-free in the absence of radiotherapy was 0.66 (combined estrogen-receptor-positive/ estrogen-receptor-negative).
Conclusions: 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.

LU TP 07-17