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

摘要: Background Breast cancer patients who are resistant to neoadjuvant chemotherapy (NeoCT) have a poor prognosis. There is pressing need develop in vivo models of chemo tumors test novel therapeutics. We hypothesized that patient-derived breast xenografts (BCXs) from chemo- naive and chemotherapy-exposed can provide high fidelity for chemoresistant cancers. Methods Patient BCXs were characterized with short tandem repeat DNA fingerprinting, reverse phase protein arrays, molecular inversion probe next generation sequencing. Results Forty-eight cancers (24 post-chemotherapy, 24 chemo-naive) implanted 13 established (27%). BCX engraftment was higher TNBC compared hormone-receptor positive (53.8% vs. 15.6%, p = 0.02), received NeoCT (41.7% 8.3%, had progressive disease on (85.7% 29.4%, 0.02). Twelve developed metastases after surgery; five, before distant relapse. Patients whose lower recurrence-free survival (p 0.015) overall (p<0.001). Genomic losses gains could be detected the BCX, three demonstrated transformation induce mouse tumors. However, overall, somatic mutation profiles including potential drivers maintained upon implantation serial passaging. One model cultured vitro re-implanted, maintaining its genomic profile. Conclusions BCXs clinically aggressive cancers, especially response NeoCT. Future studies will determine identification genotype-phenotype correlations individualization treatment.