Adrian Lee      

Professor; Pittsburgh Foundation Chair in Precision Medicine, Professor, Department of Pharmacology and Chemical Biology, University of Pittsburgh

GENOMIC LANDSCAPE OF BREAST CANCER RELAPSE AND METASTASIS

It is now clear that breast cancers evolve and adapt as they progress and metastasize. Drug treatment influences evolution and selects for drug resistance mutations. The ability of a breast cancer to adapt may highlight novel dependencies which are clinically targetable. We are examining breast cancer evolution using tissue and liquid biopsies during treatment of advanced disease and also by rapid autopsy. A major finding from these studies is the gain of mutations (single nucleotide aberration, fusions and copy number aberrations) in estrogen receptor (ESR1) in hormone-refractory metastatic disease. While these changes likely have clinical importance – there are other passenger mutations that can be used to understand the natural history of the disease and response to therapy. I will discuss our studies on evolution in breast cancer using rapid autopsy, and provide an introduction to the BCRF Aurora program which is performing comprehensive molecular profiling of primary and metastatic breast cancer.