ATYPICAL RESPONDERS LANDSCAPE REVIEW ∙ OCTOBER, 2017 10 The strengths of this definition are that it is quantifiable and applicable to commonly measured outcomes (CR, PFS, and overall survival) [4]. The AURORA (Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer) initiative for MBC is a program of the Breast Cancer Research Foundation (BCRF) Founder’s Fund for Metastasis Research that includes European and US clinical trials. AURORA EU is a collaborative effort among the Breast International Group, Breast European Adjuvant Studies Team, and Frontier Science & Technology Research Foundation, Inc. Its purpose is to increase genomic and clinical knowledge generated from MBC patients [5]. Initially, 1,300 MBC patients who are either newly diagnosed or have been treated with no more than one line of systemic treatment in the metastatic setting will be recruited to this prospective trial. In this study, primary and metastatic tumors as well as blood and plasma samples will be subjected to molecular testing to increase understanding of the molecular evolution of breast cancer. A key goal of this research is to identify predictive biomarkers for response and resistance to commonly applied anticancer agents. Towards that end, a subset of patients in the AURORA study who are characterized as “exceptional responders” or “rapid progressors” will be subjected to more extensive molecular testing to identify prognostic and predictive biomarkers. Another study objective is to provide evidence supporting the feasibility of a global molecular screening platform for MBC. The US- based counterpart to the AURORA project, led by Dr. Nancy Davidson of the University of Pittsburgh and conducted by the Translational Breast Cancer Research Consortium led by Dr. Antonio C. Wolff of Johns Hopkins University, will conduct a prospective trial similar to AURORA EU. They will also perform a retrospective analysis of banked paired primary and metastatic specimens, together with a translational laboratory component utilizing patient-derived xenograft models to study metastatic disease. The strengths of the AURORA study include the molecular testing approach, the consideration of a possible global molecular screening platform, the incorporation of rapid progressors, and quantifiable definitions of both exceptional responders and rapid progressors. A limitation is not considering lifestyle, co-morbidities, or other potential contributing factors that may impact a therapeutic response. AURORA endeavors to examine both spectrums of MBC patients exhibiting an atypical response. The study defines exceptional responders as those “showing (nearly) complete response for a duration exceeding 1 year” and rapid progressors as “patients on first- or second-line treatment progressing within the first 3 months since its initiation.” [5]. Notable strengths of this definition are the attempt at quantification and the specific inclusion of rapid progressors.