Abstract 5635: Joint secondary transcriptomic analysis of triple negative breast cancer offers a window into new therapeutic possibilities and biomarkers

Abstract

Abstract Breast cancer is a harmful growth of mutated breast tissue that is diagnosed in 2.3 million women yearly, and kills 685,000 patients (15%) each year around the world. Left unchecked, breast cancer can grow proliferatively and metastasize to new tissue sites, monopolizing the body’s energy supply and ultimately causing organ failure and death. Due to increased use of treatments targeting the breast tumor-specific markers Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2), patient survival of breast cancer has increased in recent years. However, patients with triple-negative breast cancer (TNBC), tumors lacking all three commonly-targeted biomarkers, suffer greater illness, experience more frequent relapse, and enjoy a shorter lifespan compared to other breast cancer patients due to the paucity of tumor-selective treatments for TNBC. Further research on TNBC is needed to understand targetable mechanisms and develop treatments capable of targeting the key mechanisms. To investigate the transcriptomic profiles of TNBC tumors, we performed a joint secondary analysis of publicly available RNA-sequencing data for TNBC, consisting of 214 relevant samples across 11 distinct studies in the NCBI Gene Expression Omnibus (GEO). We found ~12,500 significant differentially expressed genes (FDR p-value ⇐ 0.05) and 67 significantly modulated pathways (FDR p-value ⇐ 0.05). Additionally, our novel findings include candidates for drug repurposing, high-integrity predictive biomarkers, and potential new TNBC molecular mechanisms. We found several TNBC drug targets that have not yet been fully leveraged along with drugs that could likely be successfully repurposed for use in TNBC based on previous target history and our transcriptomic results. This joint secondary analysis opens the door to future therapeutic options that could increase patient survival once validated in the wet lab. Citation Format: Naomi Rapier-Sharman, Jenna Birchall Poulsen, Mauri E. Dobbs, Brett E. Pickett. Joint secondary transcriptomic analysis of triple negative breast cancer offers a window into new therapeutic possibilities and biomarkers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5635.