A breast cancer patient-derived xenograft biobank for precision medicine studies in Argentina

PATACCINI, GABRIELA; ELIAS, ANDRES; ROJAS, PAOLA; SEQUEIRA, GONZALO R.; LAMB, CAROLINE A.; FIGUEROA, VIRGINIA; MARTÍNEZ VÁZQUEZ, PAULA; BURRUCHAGA, JAVIER; SPENGLER, EUNICE; LIGUORI, MARCOS; GASS, HUGO; VANZULLI, SILVIA; ABBA, MARTIN; LANARI, CLAUDIA

Congreso; Buenos Aires Breast Cancer Symposium; 2021

Patient-derived tumor xenografts (PDX) are generated by implanting tumor fragments directly from patients into immune-deficient mice. PDX reflect more accurately the human tumor biology as compared with cell line xenografts, since the latter have acquired different portraits due to long term culturing. Our aim was to establish a bank of genetically characterized breast cancer PDX models for precision medicine studies. The study was approved by Institutional IRB (021-2017). Surgical specimens from patients that attended ?Magdalena V de Martinez Hospital? from General Pacheco were transplanted sc by trocar into estradiol (E2)-treated (0.5 mg pellets, sc) or untreated female NSG mouse. Once the tumors reached 0.8 cm in diameter (long axis), they were excised, frozen, formalin-embedded for diagnosis, and passaged in E2-treated or untreated mice. A total of 95 samples were transplanted, and 9 PDX were developed: 2 luminal B, 1 luminal B that changed to triple negative (TN), 1 HER2 and 5 TN. Seven PDX were studied by Exome-Seq. Relevant mutations in FGFR1, ERBB2, STAT5A, FOXA1, BRCA1, PIK3CA, WNT4 and others were registered in the different PDXs. MUC2-19, HDAC6, HDAC7, Serpina2, LAIR1 among others were mutations present in almost all PDX. We conclude that these models are valid preclinical tools to test therapeutic efficacy of existing or novel drugs to guide breast cancer treatment.