Characterization of a luminal B and a HER2 breast cancer patient-derived xenograft

GABRIELA PATACCINI; MARCELA COIANIS; RAMIRO PERROTTA; SILVIA VANZULLI; CLAUDIA LANARI; CAROLINE A. LAMB

Mar del Plata

Congreso; Sociedad argentina de investigación clínica; 2021

Molecular classification of breast cancer (BC) includes four main subtypes defined as luminal A and B, both of which express estrogen receptor alpha (ERα); HER2+-enriched, which overexpress HER2 and are ERα-, and triple negative (TN) tumors, which are ERα-/HER2-. Patient-derived tumor xenografts (PDX) are generated by implanting tumor fragments directly from patients into immune-deficient mice. This model reflects more accurately the human tumor biology as compared with cell line xenografts and have potential applications in precision medical treatments. We have recently established and genetically characterized 9 PDX (2 luminal, 1 HER2+, and 6 TN) derived from BC patients from Hospital Magdalena V. de Martínez. The aim of this study was to characterize one of the luminal PDX (707) and the HER2+ PDX (474) in terms of biomarker expression and treatment response to be used as models of these BC subtypes. PDX707 and the parental tumor are both ER+/PR-/HER2-, while PDX474 and its parental tumor are ER-/PR-/HER2+. Androgen receptor (AR) expression was also evaluated being both PDXs AR+. PDX707 was treated with tamoxifen (TAM; 5 mg/kg/5 days a week, sc) or testosterone (TESTO; 20 mg pellet, sc) and PDX474 with trastuzumab (TZ) and TZ emtansine (TDM1; 15 mg/kg/3 days a week, sc). Treatments started when tumors were 25 mm2. TAM and TESTO inhibited PDX707 tumor growth (p