Toward individualized breast cancer therapy: translating biological concepts to the bedside

The management of breast cancer has changed dramatically over the past 20 years. Based on gene expression profiles, or proteomics of three or four biomarkers, it is apparent that there are multiple subtypes with different clinical characteristics, clinical courses, and sensitivities to existing therapies. This manuscript reviews the management of hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative breast cancers, emphasizing changes that have occurred in recent years and focusing on potential mechanisms of drug resistance. I also highlight strategies to prevent or overcome resistance to specific therapeutic agents. As a result of enhanced biological understanding of the molecular anomalies that drive the development, progression, and dissemination of breast cancer, a number of novel, molecularly targeted agents have been added to standard therapies. Chemotherapy, endocrine therapy, and targeted treatments have markedly reduced the risk for recurrence and mortality after primary treatment of breast cancer and have increased the 5- and 10-year survival rates. The challenges with novel therapeutics include the absence of accurate predictive biomarkers to identify those patient who will derive substantial benefit and those patients whose tumors are resistant to specific antitumor agents. As we move forward with increasing molecular segmentation of breast cancer and develop new, highly targeted agents, molecular diagnostics must accompany molecular therapeutics to implement the concept of personalized cancer therapy.