Ability to Generate Patient-Derived Breast Cancer Xenografts Is Enhanced in Chemoresistant Disease and Predicts Poor Patient Outcomes

PloS One
Priscilla F McAuliffeFunda Meric-Bernstam

Abstract

Breast cancer patients who are resistant to neoadjuvant chemotherapy (NeoCT) have a poor prognosis. There is a pressing need to develop in vivo models of chemo resistant tumors to test novel therapeutics. We hypothesized that patient-derived breast cancer xenografts (BCXs) from chemo- naïve and chemotherapy-exposed tumors can provide high fidelity in vivo models for chemoresistant breast cancers. Patient tumors and BCXs were characterized with short tandem repeat DNA fingerprinting, reverse phase protein arrays, molecular inversion probe arrays, and next generation sequencing. Forty-eight breast cancers (24 post-chemotherapy, 24 chemo-naïve) were implanted and 13 BCXs were established (27%). BCX engraftment was higher in TNBC compared to hormone-receptor positive cancer (53.8% vs. 15.6%, p = 0.02), in tumors from patients who received NeoCT (41.7% vs. 8.3%, p = 0.02), and in patients who had progressive disease on NeoCT (85.7% vs. 29.4%, p = 0.02). Twelve patients developed metastases after surgery; in five, BCXs developed before distant relapse. Patients whose tumors developed BCXs had a lower recurrence-free survival (p = 0.015) and overall survival (p<0.001). Genomic losses and gains could be detected in the BCX, and three m...Continue Reading

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Citations

May 8, 2016·The Journal of Steroid Biochemistry and Molecular Biology·Noriko KanayaShiuan Chen
Mar 5, 2020·The Journal of Pathology·Steven HaywardFedor Berditchevski
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Jan 9, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ming ZhaoFunda Meric-Bernstam
Jul 6, 2021·Annual Review of Cancer Biology·Cristina E TognonJeffrey W Tyner

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Methods Mentioned

BETA
xenografts
biopsy
dissection
xenograft
genotyping
biopsies
exome sequencing
protein array
PCR

Software Mentioned

Affymetrix
samtools
VarScan2
GeneCycle
BWA
ClassComparison
R

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