Cancer Evolution as the New Frontier of Precision Medicine.

New experimental breast cancer therapies directed against novel targets are currently in clinical These experimental agents are likely to be effective for a niche of breast cancers with specific "driver mutations". The ability to perform comprehensive molecular profiling of individual tumors has rapidly expanded over the last few years, and new DNA sequencing technologies require relatively limited quantities of fresh or archived paraffin-embedded or snap-frozen tumor tissue and provide rapid turnaround of sequencing results within a few weeks or less. All these technologies provide an unprecedented opportunity to identify patients with rare "driver" molecular alternations that are candidates for proof-of-concept clinical trials with matched targeted therapy, in the context of basket trials. The aim of this chapter on molecular profiling is to summarize the known recurrent molecular alterations in breast cancer that are potentially amenable to investigational targeted therapy, to provide an overview of the existing technological platforms for molecular profiling and ongoing or planned institutional/national screening initiatives and to outline a vision for molecular screening that may be integrated into the future activities of breast cancer research.