32 Clinical Trials Analysis We extracted clinical trials information on all phase I, II, and III breast cancer treatment trials that were recruiting patients with MBC in the United States (US) in April and May 2014 from the NCI PDQ database, which imports information on all cancer trials registered in ClinicalTrials.gov. We also included trials in solid tumors if they were tagged for breast cancer and therapeutic trials that targeted patients with BRCA mutations (associated with hereditary breast cancer), regardless of metastatic status. We manually categorized these trials (into a single category, even if potentially applicable to > 1) according to whether their interventions were a targeted therapy, chemotherapy, or therapy directed at a specific metastatic site such as brain, liver, or bone. Targeted therapies were defined as agents that block the growth and spread of cancer by interfering with specific molecules (“molecular targets”) involved in the growth, progression, and spread of cancer[8] . The targeted-therapy trials were further manually assigned to the Hallmarks of Cancer framework[5] . For each study, we also captured the investigational agent and its biological target (where appropriate), required tumor biomarkers, and trial phase. We reviewed the list in August 2014 to note trials that were no longer recruiting patients, as noted in Appendix 1. Figure 1: Hallmarks of Cancer Framework by Hanahan and Weinberg[5] Used for Trials Hallmarks of Cancer: The Next Generation DEREGULATING CELLULAR ENERGETICS SUSTAINING PROLIFERATIVE SIGNALING ENABLING REPLICATIVE IMMORTALITY TUMOR-PROMOTING INFLAMMATION ACTIVATING INVASION & METASTASIS INDUCING ANGIOGENESIS EVADING GROWTH SUPPRESSORS AVOIDING IMMUNE DESTRUCTION GENOME INSTABILITY AND MUTATION RESISTING CELL DEATH