Patient-derived xenograft (PDX) models of
breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and
biomarker identification. We established orthotopic PDX models of
triple negative breast cancer (TNBC) from the primary
breast tumors of patients prior to and following
neoadjuvant chemotherapy (NACT) while they were enrolled in the ARTEMIS trial (NCT02276443). Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of
Adriamycin and
cyclophosphamide (AC, mid-NACT), and in cases of AC-resistance, after a 3-month course of different
experimental therapies and/or additional
chemotherapy (post-NACT). Our study cohort includes a total of 269 fine needle aspirates (FNAs) from 217 women, generating a total of 62 PDX models (overall success-rate = 23%). Success of PDX engraftment was generally higher from those
cancers that proved to be treatment-resistant, whether poorly responsive to AC as determined by ultrasound measurements mid-NACT (p = 0.063), RCB II/III status after NACT (p = 0.046), or metastatic relapse within 2 years of surgery (p = 0.008). TNBC molecular subtype determined from gene expression microarrays of pre-NACT
tumors revealed no significant association with PDX engraftment rate (p = 0.877). Finally, we developed a statistical model predictive of PDX engraftment using percent Ki67 positive cells in the patient's diagnostic biopsy, positive lymph node status at diagnosis, and low volumetric reduction of the patient's
tumor following AC treatment. This novel bank of 62 PDX models of TNBC provides a valuable resource for
biomarker discovery and preclinical therapeutic trials aimed at improving neoadjuvant response rates for patients with TNBC.