Establishment of a metastatic patient-derived xenograft model of breast carcinoma.

Abstract

In this study, we investigated the development and application of patient-derived xenograft (PDX) models for metastatic breast carcinoma. Orthotopic PDX models were established from tumor tissue of invasive ductal breast carcinoma patients without prior neoadjuvant therapy. Following successful tumor engraftment in immunodeficient NOD SCID gamma (NSG) mice, primary tumors were surgically excised using a procedure simulating radical mastectomy, enabling extended post-operative survival for the development of eventual metastases. Tumor growth, the presence of lung metastases, along with their histopathological features and immunohistochemical profiles, were evaluated. Three stable and transplantable PDX models were successfully established. Spontaneous lung metastases developed in one model following surgical resection, and this metastatic capability was preserved across multiple in vivo passages. Despite the successful engraftment, significant discrepancies were observed between the immunohistochemical characteristics of the original patient tumors and their corresponding PDXs, particularly in hormone receptor status and Ki-67 proliferation marker expression. These findings highlight the challenges of maintaining molecular fidelity in traditional PDX models.