The Role of Genomic Profiling in Advanced Breast Cancer: The Two Faces of Janus.

Abstract

Recent advances in genomic technology have led to considerable improvement in our understanding of the molecular basis that underpins breast cancer biology. Through the use of comprehensive whole genome genomic profiling by next-generation sequencing, an unprecedented bulk of data on driver mutations, key genomic rearrangements, and mechanisms on tumor evolution has been generated. These developments have marked the beginning of a new era in oncology called "personalized or precision medicine." Elucidation of biologic mechanisms that underpin carcinogenetic potential and metastatic behavior has led to an inevitable explosion in the development of effective targeted agents, many of which have gained approval over the past decade. Despite energetic efforts and the enormous support gained within the oncology community, there are many obstacles in the clinical implementation of precision medicine. Other than the well-known biologic markers, such as ER and Her-2/neu, no proven predictive marker exists to determine the responsiveness to a certain biologic agent. One of the major issues in this regard is teasing driver mutations among the background noise within the bulk of coexisting passenger mutations. Improving bioinformatics tools through electronic models, enhanced by improved insight into pathway dependency may be the step forward to overcome this problem. Next, is the puzzle on spatial and temporal tumoral heterogeneity, which remains to be solved by ultra-deep sequencing and optimizing liquid biopsy techniques. Finally, there are multiple logistical and financial issues that have to be meticulously tackled in order to optimize the use of "precision medicine" in the real-life setting.