A prognostic DNA signature for T1T2 node-negative breast cancer patients

Abstract

Predicting evolution of small node-negative breast carcinoma is a real challenge in clinical practice. The aim of this study was to search whether qualitative or quantitative DNA changes may help to predict metastasis of small node-negative breast carcinoma. Small invasive ductal carcinomas without axillary lymph node involvement (T1T2N0) from 168 patients with either good (111 patients with no event at 5 years after diagnosis) or poor (57 patients with early metastasis) outcome were analyzed with comparative genomic hybridization (CGH) array. A CGH classifier, identifying low- and high-risk groups of metastatic recurrence, was established in a training set of 78 patients, then validated, and compared with clinicopathological parameters in a distinct set of 90 patients. The genomic status of regions located on 2p22.2, 3p23, and 8q21-24 and the number of segmental alterations were defined in the training set to classify tumors into low- or high-risk groups. In the validation set, in addition to estrogen receptors and grade, this CGH classifier provided significant prognostic information in multivariate analysis (odds ratio, 3.34; 95% confidence interval 1.01-11.02; P = 4.78 × 10(-2), Wald test). This study shows that tumor DNA contains important prognostic information that may help to predict metastasis in T1T2N0 tumors of the breast.