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Series GSE216333 Query DataSets for GSE216333
Status Public on Jan 12, 2023
Title Predictors of success in establishing orthotopic patient-derived xenograft models of triple negative breast cancer
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, with approximately 50% of patients having residual disease after neoadjuvant chemotherapy (NACT) and worse prognosis with higher residual cancer burden (RCB). Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. There is a need for PDX models encompassing the heterogeneity of TNBC both pre- and post- therapy and for identifying clinical and molecular features of patient’s tumors that are associated with success in establishing these models. Using fine-needle aspirates (FNAs), we established orthotopic PDX models of TNBC from the primary breast tumors of patients prior to and following neoadjuvant systemic therapy while enrolled in the ARTEMIS trial (NCT02276443). ARTEMIS is a prospective neoadjuvant clinical trial for women with primary TNBC who are treated with four cycles of Adriamycin combined with cyclophosphamide (AC) followed by taxane +/- different experimental therapies. Serial biopsies were obtained from patients prior to treatment (pre-therapy), from poorly responsive disease after four cycles of AC (mid-NACT), and in cases of AC-resistance, after a three-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a total of 269 FNA biopsies from 217 women, generating a total of 62 successful PDX models (overall success-rate = 23%). This cohort includes five serial pre- and mid-NACT PDX pairs, as well as one serial pre-, mid-, post-NACT triplet. Success of PDX engraftment was generally higher from cancers that proved to be treatment-resistant: whether poor response to AC determined by ultrasound measurements mid-NACT (p=0.063), RCB II/III status after NACT (p=0.046), or metastatic relapse within two years of surgery (p=0.008). TNBC molecular subtype determined from gene expression microarrays of pre-NACT tumor 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.
 
Overall design We established 207 treatment-naïve patient-derived xenograft tumors from triple negative breast cancer tumors and profiled the gene expression profiles on Affymetrix microarrays.
 
Contributor(s) Echeverria GV, Cai S, Tu Y, Shao J, Powell E, Redwood AB, Jiang Y, McCoy A, Rinkenbaugh AL, Lau R, Trevarton AJ, Fu C, Gould R, Ravenberg EE, Huo L, Candelaria R, Santiago L, Adrada BE, Lane DL, Rauch GM, Yang WT, White JB, Chang JT, Moulder S, Symmans WF, Hilsenbeck SG, Piwnica-Worms H
Citation(s) 36627285
Submission date Oct 21, 2022
Last update date Jan 12, 2023
Contact name Jeffrey Chang
E-mail(s) jeffrey.t.chang@uth.tmc.edu
Organization name University of Texas
Street address 6431 Fannin St
City Houston
ZIP/Postal code 77019
Country USA
 
Platforms (1)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
Samples (207)
GSM6670322 pdx_breast_tumor_ATID002
GSM6670323 pdx_breast_tumor_TNBC001
GSM6670324 pdx_breast_tumor_TNBC004
Relations
BioProject PRJNA893001

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE216333_RAW.tar 416.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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