Abstract B19: Breast cancer patient-derived xenografts: The University of Illinois at Chicago Cancer Center experience

Abstract

Abstract Introduction: The purpose of this study was to create the first ever breast cancer patient-derived xenograft (PDX) model at the University of Illinois at Chicago (UIC) Cancer Center available to all breast cancer investigators. The intention is to provide opportunities to perform preclinical trials of lead cancer drugs as well as to conduct racial disparity studies. Methods: All patient tissues were collected from informed, consented patients with an IRB approved protocol (#14-1078) and with compliance of HIPAA law. None of the patients received neoadjuvant chemotherapy. Within 30 minutes of surgical excision, each tumor specimen was bilaterally implanted into the 2nd thoracic mammary fat pad of two NOD/SCID/IL2γ-receptor null (NSG) mice. Additional tissue was placed in RNAlater for gene expression analysis in successful engraftments. Transplantation sites were monitored daily for one week and measured weekly with calipers using the formula l x w2/2. Formalin-fixed and paraffin embedded sections (5 μm) were stained with hematoxylin and eosin (H&E) for histological examination. Immunohistochemical (IHC) staining was performed with ERα (SP1), CD20 (L26), and keratin cocktail (AE1/3) antibodies (Ventana). Results: Between April and August 2015, a total of eleven primary breast cancer PDXs were engrafted from eight African-American, two Caucasian and one patient of unknown race. The subtypes represented in these primary engraftments included one triple-negative breast cancer (TNBC), eight estrogen receptor alpha positive (ERα+) and two HER2 positive (HER2+) PDXs. Five primary PDXs engrafted successfully and were passaged to second generation mice including one TNBC and four ERα+ PDXs. After 12 weeks of primary engraftment, UIC-PDX#6 (ERα+) PDX grew at a much faster rate than any of the other PDXs and was passaged twice. Following the second passage, tumor tissue was processed for histological examination when it was discovered the PDX was not a tumor of epithelial origin, but was in fact a tumor of B-cell origin. This finding is in agreement with the recent report by Bondarenko et. al. (Neoplasia, 2015) that B-cell lymphomas frequently occur in PDXs engrafted into NSG mice. At the time of this writing, the remaining TNBC and ERα+ PDXs are growing at a slower pace in the second passage NSG mice and two additional primary PDXs are growing and nearing secondary passage. Conclusions: A breast cancer PDX effort was initiated at UIC from a racially diverse patient population. Despite engraftment of a B-cell tumor in one PDX, four promising stable breast cancer PDXs are currently being maintained. We have plans to test and validate novel endocrine therapies as well as other promising strategies to treat breast cancer. Citation Format: Huiping Zhao, Thao Pham, Rajyasree Emmadi, Elizabeth Wiley, Michael Warso, Alejandra Perez-Tamayo, George Salti, Kent Hoskins, Debra A. Tonetti. Breast cancer patient-derived xenografts: The University of Illinois at Chicago Cancer Center experience. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B19.