Personalizing Breast Cancer Treatment with Patient-derived Xenografts (PDX): Analyzing PDXs Fidelity, Stability, and Intra-Tumoral Heterogeneity

Breast cancer (BC) is a complex disease with varied histology and molecular behaviors. Patient-derived xenografts (PDXs) have been developed to study tumor progression and personalized treatment strategies. Here, we assessed the stability and fidelity of BC PDXs in maintaining key characteristics of their source biopsies across generations and various engraftment sites in mice. Using NSG-SGM3 mice, we established PDX models from primary tumors of 22 patients, creating three luminal A subtype models. Our results showed high concordance in histopathological and molecular profiles between the PDXs and their corresponding biopsies. PDX engraftment success was linked to the aggressiveness of patients' tumors and specific gene expressions. We found strong correlations with genes associated with intrinsic tumor pathways and variability related to immune responses. Our findings highlight the effectiveness of BC PDXs in replicating patient tumors and provide insights into factors affecting engraftment, growth, and stability, enhancing their role in personalized BC research.