Abstract 47: Optimizing in vivo establishment of hormone receptor-positive breast cancer patient-derived xenografts for therapeutic assessment

Abstract Patient-derived xenograft (PDX) models are invaluable tools for studying the heterogeneity of primary human tumors and preclinical drug responses. However, traditional PDX models for estrogen receptor-positive (ER+) breast cancer face notable challenges. These models involve implanting tumor tissue into mice with the aim of achieving tumor "engraftment, " a process that typically requires 2 to 6 months and often longer for the tumor to grow to a size adequate for passaging. This extended timeframe, combined with the relatively indolent and less aggressive nature of hormone receptor-positive (HR+) breast cancers, results in lower success rates for tumor engraftment and passage. Additionally, these slow-growing tumors are prone to clonal selection during long-term growth, further reducing the utility of traditional PDX models for timely therapeutic studies. To address these challenges, we developed a streamlined PDX model optimized for HR+ breast cancer. Tumors were resected from deidentified patients at Karmanos Cancer Institute meeting specific eligibility criteria: ER or PR-positive, HER2-negative, and no prior neoadjuvant or endocrine therapy. Tumor specimens were aseptically implanted into the mammary fat pads of female SCID mice, which were supplemented with slow-release estradiol pellets to maintain estrogen levels. Tumor growth was monitored using caliper measurements, and tumor presence and vascularization were confirmed at 14 days post-implantation using Susceptibility Weighted Imaging (SWI). Following confirmation of tumor establishment, mice were randomized into two groups: a Tamoxifen-treated cohort (100 mg/kg orally for three days) and an untreated control group. Tumors were subsequently harvested for molecular and histological analyses. Our preliminary findings indicate that tumor engraftment and vascularization can be reliably achieved within two weeks, supporting the feasibility of this approach for time-sensitive therapeutic studies. Importantly, tumors remained present following treatment, providing adequate samples for downstream analyses after the experiment. This model circumvents many limitations of traditional PDX systems, including slow tumor growth and clonal selection, while providing a practical platform for studying endocrine therapy responses in HR+ breast cancer. By minimizing reliance on long-term engraftment and optimizing conditions for short-term assessment, this refined system holds promise for advancing translational research and improving preclinical evaluations of HR+ breast cancer therapies. Citation Format: Abigail M. Fielder, Manohar Ratnam, Lisa Polin, Julie Boerner, Seongho Kim, Kristen Purrington. Optimizing in vivo establishment of hormone receptor-positive breast cancer patient-derived xenografts for therapeutic assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 47.