Successes and limitations of targeted cancer therapy in breast cancer.

Breast cancer is not a single disease. Specific biological processes and distinct genetic pathways are associated with prognosis and sensitivity to chemotherapy and targeted agents in different subtypes of breast cancers. As a consequence, breast cancer can be classified by molecular events. A primary challenge for future drug development in breast cancer will be to distinguish genes and pathways that 'drive' cancer proliferation (drivers) from genes and pathways that have no role in the development of cancer (passengers). The identification of functional pathways that are enriched for mutated genes will select subpopulation of patients likely to be sensitive to biology-driven targeted agents. The selection of driver pathways in resistant tumors will permit to discover a biology-driven platform for new drug development to overcome resistance. We are moving in the era of stratified and personalized therapy. Personalized cancer therapy is based on the precept that detailed molecular characterization of the patient's tumor and its microenvironment will enable tailored therapies to improve outcomes and decrease toxicity. However, there are numerous challenges we need to overcome before delivering on the promise of personalized cancer therapy. These include tumor heterogeneity and molecular evolution, costs and potential morbidity of biopsies, lack of effective drugs against most genomic aberrations, technical limitations of molecular tests, and reimbursement and regulatory hurdles. Critically, successes and limitations surrounding personalized cancer therapy must be tempered with realistic expectations, which, today, encompass increased survival times for only a portion of patients.