Addressing Therapy Resistance in Metastatic Breast Cancer

Project goals:

• To determine factors of treatment resistance to precision medicines
• (including immunotherapies) by correlating genomic and stromal features with detailed treatment histories.
• To validate identified factors of resistance in PDXs derived from matched MBCs.
• To provide data about the spatial and temporal heterogeneity of MBC.
• To return the genomic profile readout to oncologists for real-time clinical decision making and for enrollment in precision-tailored clinical trials.

Summary:

The characterization of metastatic breast cancer (MBC) is critical to understand how to select therapy that can improve survival of patients with MBC. Tumors evolve during the metastatic process, acquire new mutations, alter target protein expression, as they learn to adapt to novel environments in different anatomical sites and to survive different anti-cancer drugs.  Our hypothesis is that the interaction between the evolving tumor and its metastatic microenvironment plays an important role in mediating treatment resistance in MBC. One of the bottlenecks in our understanding of MBC is the limited accessibility to high quality clinically annotated metastatic breast tumor samples. The MOHCCN initiative presents an exciting opportunity to bring together a unique team of investigators and consortia to enable an in-depth analysis of MBC. We propose to make use of already established breast tissue banking infrastructures to continue the generation of a unique collection of MBC samples with updated clinical data ready to be profiled. In total, our group will bring close to 500 MBC samples including 155 freshly frozen (FF) clinically annotated samples ready for genomic profiling. We will combine whole genome tumor analysis with stromal and immune profiling (mass cytometry) in treatment-annotated clinical samples.