ES2-3: Patient-Derived Xenograft Models for Preclinical Breast Cancer Research: Not Just "Basal" Anymore.

Abstract

Abstract Translational breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect the range of patient tumor biology accurately. In an effort to overcome these limitations, several groups have recently succeeded in propagating patient-derived breast cancer xenografts representing multiple breast cancer subtypes, including estrogen and progesterone receptor positive, and HER2 positive tumors. In our laboratory, we have developed a diverse set of human breast tumors grown as xenografts in the mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null (NSG) mice, two relatively new immunocompromised mouse models, under various transplant conditions. In all cases, xenograft lines were established directly from breast cancer patient samples, without intervening culture in vitro, using the epithelium-free mammary fat pad as the transplantation site. Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet without exogenous human fibroblasts. Thirty five stably transplantable xenograft lines representing 27 patients were established, using pre-treatment, mid-treatment, and/or post-treatment samples. Most patients yielding xenografts were “triple-negative” (ER−PR-HER2−) (n=21). However, we were able to establish lines from three ER−PR-HER2+ patients, one ER+PR+HER2−, one ER+PR-HER2−, and one “triple-positive” (ER+PR+HER2+) patients. Serially passaged xenografts show phenotypic consistency with the tumor of origin at the histopathology level, and remarkable stability across multiple transplant generations at both the genomic, transcriptomic, and proteomic levels. Of 27 lines evaluated fully, thirteen xenografts showed metastasis to the mouse lung. These models, in conjunction with others like them, thus serve as renewable, quality-controlled tissue resources, and are proving useful for preclinical evaluation of experimental therapeutics. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES2-3.