Abstract 2919: Novel pre-clinical model to identify genetic modifiers of triple negative breast cancer

Abstract

Abstract Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor outcomes. This is a grave clinical challenge for the ~30,000 patients diagnosed with this disease every year. Discovering genetic modifiers of differential TNBC vulnerability and disease progression is critical to improving predictive and personalized treatments. We hypothesized that using a well-established recombinant inbred strain, novel genetic modifiers of TNBC risk and aggression will be identified. The C3(1)-T antigen (C3Tag) genetically engineered mouse model (GEMM) recapitulates many facets of human basal-like TNBC to demonstrate promoting effects of exposures on tumor phenotypes. However, GEMM are highly constrained by their inbred genotype and do not allow a robust interrogation of the manner in which individual genetic variation might impact tumor initiation, progression, and response to therapy. Therefore, we developed a novel murine model of TNBC in the background of the largest and best characterized genetic reference population. Systems genetics is used to identify gene candidates. Cross-species comparison of our findings with publicly available human GWAS and genomic databases is an effective approach to validate conserved biologically relevant and targetable pathways. To our knowledge, this is the first study to explore modifier genes for TNBC phenotypes using a systems genetics approach in a GEMM for TNBC. Our results will contribute to significant advances in understanding risk and improving outcomes for breast cancer. Citation Format: Laura M. Sipe, Emily B. Korba, Lu Lu, Robert W. Williams, David G. Ashbrook, Liza Makowski. Novel pre-clinical model to identify genetic modifiers of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2919.