Abstract C88: Genomics, advocacy, and emerging therapeutics to address triple-negative breast cancer (TNBC) outcome disparities.

Background: Collaborative team science provides a starting point for comprehensive change, and advocates have a unique and important role developing and engaging in transdisciplinary collaboratives that focus on new questions and new possibilities to advance the science of ethnic and medically underserved health care disparities. Participating in four areas : 1) research and programmatic support, 2) education and outreach, 3) policy and strategy, and 4) representation and advisory, the UCSF Breast Science Advocacy Core (BSAC) Program, a volunteer affiliate of the Breast Oncology Program (BOP), one of ten multidisciplinary research programs under the umbrella of the UCSF Helen Diller Comprehensive Cancer Center promotes a transformative, transdisciplinary, integrated environment to study the biological basis of the diseases that comprise breast cancer; to define the risk of developing or progressing with specific types of breast cancer; to develop novel interventions that work locally and globally to reduce morbidity and mortality from breast cancer and its treatment; and to leverage new collaborative research, education, and mentoring/training opportunities that address cancer outcome disparities. Advocates involved in KOMEN, DOD, PCORI, AND CBCRP funded research and training grants apply four core principles that forge synergy with NCI Advocacy Research Working Group Recommendations: 1)strategic innovation, 2)collaborative execution, 3)evidence based decision-making, and 4) ethical codes of conduct. Embracing transdisciplinary professionalism, researchers and advocates build on their track record as shared value partners committed to furthering the collective impact of science advocacy exchange (SAE). Study Objectives: Genomic analyses of patient tumors have unearthed an overwhelming number of recurrent somatic alterations in genes that have dramatic effects on tumor biology, patient drug responses, and clinical outcomes. In one study, high grade triple negative breast cancer (TNBC) accounts for 34% of breast cancers in African American women versus 21% in white women. A growing body of evidence has shown that African American women have biologically more aggressive disease, independent of social determinants, and suffer the highest mortality rates. While biological breakthroughs of the last decade have greatly advanced our understanding of cancer, in advanced TNBC, a poor prognosis subtype, there is an urgent need to translate this evolving patient genomic data into new therapeutic paradigms. Our study focuses on the intersection of synthetic lethal approaches, MYC driven human cancers, and immunotherapy as an “innovation agenda”. A distinct MYC vision highlights how overexpression is associated with aggressive outcomes and poor patient outcomes, and synthetic lethal strategies to target MYC (CDK inhibitors, PIM2, as well as the PDI immune pathways) have potential for addressing outcome disparities In African American Women with Triple Negative Breast Cancer (TNBC). Key Findings: We have developed a screening technique that can be used to rapidly and accurately identify potential synthetic lethal interactions in TNBC. This platform utilizes an isogenic cell line system that we have developed to model oncogene activation in TNBC. A growing body of evidence has shown that: 1) Quantitative approach maps genotype-specific drug responses in isogenic cells 2) Systematic discovery of biomarkers for cancer drugs under clinical investigation 3) Clinically actionable synthetic lethal interaction between MYC and dasatinib is discovered 4) Mechanism of dasatinib action through inhibition of LYN kinase is described Key Take-Away Message: The inclusion of advocates in convergent science settings remind academic stakeholders that research is there to benefit the patient as they attempt to spark innovation, democratize science, and support smarter interventions that expedite the incredible potential of future investments in bioscience within disparities arenas. Citation Format: Susan Samson, Alicia Y. Zhou, Maria Martins, Alexandra Corella, Dai Horiuchi, Christina Yau, Taha Rakshandehroo, John Gordan, Rebecca Levin, Jeff Johnson, John Jascur, Mike Shales, Antonio Sorrentino, Jaime Cheah, Paul Clemens, Alykhan Shamji, Stuart Schreiber, Nevan Krogan, Kevan Shokat, Frank McCormick, Sourav Bandyopadhyay, Andrei Goga. Genomics, advocacy, and emerging therapeutics to address triple-negative breast cancer (TNBC) outcome disparities. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C88.