High-resolution genomic profiling to predict 10-year overall survival in node-negative breast cancer

Women with clinically node-negative breast cancer have a better prognosis than do those with axillary lymph node metastasis. Nonetheless, ∼20% of node-negative patients die within 15 years of diagnosis, and thus additional prognostic markers are greatly needed. To identify specific copy number alterations (CNAs) that differed in frequency between 10-year survivors and deceased patients with node-negative breast cancer, array comparative genomic hybridization (aCGH) was applied to 41 primary node-negative breast tumors. Fisher's exact test was used to identify significantly different CNAs between 10-year survivors and deceased patients. Losses at 8p21.2∼p21.3, 8p23.1∼p23.2, Xp21.3, and Xp22.31∼p22.33 were significantly more common in tumors from deceased patients, suggesting that these alterations may contribute to tumor aggressiveness. Gains at 1q25.2∼q25.3 and 1q31.3∼q41 were more prevalent in tumors from survivors; specific gains at these genomic regions may inhibit further tumor progression, resulting in a less aggressive form of node-negative breast cancer. Evaluation of the identified CNAs in an independent external data set verified the prognostic potential of the 1q31.3∼q41 region. Although further extensive validation is needed, the prognostic CNAs identified in this work may in time facilitate the clinical assessment of breast cancer.