Development of a Triple-Negative Breast Cancer Model Using Patient-Derived Tumor Fragments and Study of its Response to Exposure to Chemotherapeutic Agents

Abstract

Introduction. find that triple-negative breast cancer (TNBC) is the most aggressive and difficult-to-treat subtype of breast cancer (BC), highlighting the need for the discovery and development of new drugs. Patient-derived xenograft (PDX) models are increasingly being used as model systems to test drug efficacy, as they mimic the characteristics of human tumors and their response to therapy better than other types of models.

Aim. To establish a PDX model of TNBC and characterize its sensitivity to several chemotherapeutic drugs used to treat TNBC, namely docetaxel, paclitaxel and cisplatin.

Materials and Methods. TNBC samples were obtained from 10 patients and implanted subcutaneously in immunodeficient mice. Histological examination was performed using hematoxylin and eosin staining and immunohistochemistry using antibodies against estradiol receptor, progesterone receptor and human epidermal growth factor receptor type 2. Analysis of drug sensitivity of the PDX model of TNBC was performed using the 3rd generation PDX: group 1 received paclitaxel (5 mg/kg), group 2 - docetaxel (1 mg/kg), group 3 - cisplatin (5 mg/kg), group 4 (control) - saline (n = 7 for each group). Tumor nodes were measured twice a week. The data obtained were analyzed using the STATISTICA 10.0 program; the data are presented as the mean ± error of the mean.

Results. In 3 out of 10 (30%) cases, tumor material engraftment occurred in immunodeficient mice, but only one PDX model showed stable growth as a result of successive xenotransplantations. The resulting PDX model was found to reproduce the histotype and expression pattern of estrogen receptors, progesterone receptor and HER2 receptor of the donor tumor. When exposed to docetaxel, paclitaxel and cisplatin, the tumor node volumes were 290.1 ± 22.3 mm3 (p < 0.05), 314.3 ± 20.0 mm3 and 212.3 ± 19.2 mm3, respectively, which was significantly less than the control which was 478.1 ± 50.2 mm3.

Conclusion. The resulting PDX model corresponds to the TNBC subtype and is characterized by sensitivity to todocetaxel, paclitaxel and cisplatin. This PDX model can be considered a valuable tool for research into the efficacy of new therapeutic strategies against TNBC.