Abstract 3906: Ex vivo breast tumors for understanding the patient specific tumor microenvironment remodeling and drug responses

Abstract Breast cancer is a heterogeneous disease driven by cell-intrinsic and cell-extrinsic signaling cues. Many of these cues derive from the tumor microenvironment (TME), which is composed of adipocytes, vasculature, stem cells, immune cells, and the extracellular matrix (ECM). Through these diverse components, the TME modulates cellular proliferation, survival, and ultimately response to therapy. Despite this high-level understanding of tumor-TME crosstalk, no existing pre-clinical models accurately capture the TME in vitro. We overcame that hurdle by developing a method to maintain healthy human breast tissue (HBT) alive ex vivo for at least 8 weeks. By culturing breast cancer cells in that HBT, we created ex vivo breast tumors (EVBTs) that retained patient-specific features relevant to breast cancer including menopause status, obesity status, and response to therapy. Using these EVBTs, we demonstrate breast cancer subtype-specific alterations in lipid accumulation, ECM remodeling, and cytokine profiles. RNA sequencing showed that breast cancer cell line signatures were retained in the EVBTs system at 1 week and 2 weeks in vitro. We demonstrated donor-specific transcriptional changes to the core matrisome gene set. Finally, we demonstrate that our EVBTs retained patient-specific heterogeneity in response to standard of care endocrine therapy and neoadjuvant chemotherapies. Our novel tumor model allows for 1) real-time examination of breast cancer interactions with HBT and the TME and 2) the isolation of breast cancer-specific factors vs. patient-specific factors in the development and progression of breast cancer. Citation Format: Elizabeth Martin, Megan Benz, Katie Hebert, Ethan Byrne, Frank Lau. Ex vivo breast tumors for understanding the patient specific tumor microenvironment remodeling and drug responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3906.