Despite significant progression in early diagnosis and therapeutic innovation, breast cancer is still the leading cause of cancer-related death in women worldwide. One of the difficulties for treatment improvements is the heterogeneous nature of this disease. This heterogeneity may result in partial response to chemotherapy and selection of more aggressive malignant cells. It would be of high clinical importance to characterize the molecular patterns underlying tumor evolution across the disease progression stages.In this study, we follow individual breast cancer cases at several time points, from diagnosis through post-treatment surgery till recurrence. We compare two groups of patients: patients experiencing recurrent events and patients showing no relapse for at least 7 years. Temporal molecular patterns along the therapy timeline are served to portray the evolutionary pathway that the tumors undergo throughout the path of tumor growth, therapy and recurrence. A comprehensive molecular profiling of these samples is performed by gene expression and microRNAs (miRs) expression to identify specific genes that are altered throughout this evolution. First, we profiled the expression of 800 miRs across the therapy timeline in 71samples from 20 patients. We have identified several clusters of such temporal patterns and then searched for repetitive temporal pattern along the therapy timeline between patients, indicating that these miRs might be involved in the tumor evolution towards recurrence. We then investigated the expression pattern of some miRs, known to have a role in breast cancer, and found an agreement between the expected pattern and the observed trend. We further plan to profile the mutational landscape of these tumors by DNA sequencing, in order to enrich the pictureof genetic alteration throughout tumor evolution. This knowledge will serve to identify those patients at high risk for recurrence and will immensely contribute to the advancement of personalized patient care.
