Open AccessEstablishment of chemosensitivity tests in triple-negative and BRCA-mutated breast cancer patient-derived xenograft models
Author(s) -
Hyung Seok Park,
Jeong Dong Lee,
Jee Ye Kim,
Seho Park,
Joo Heung Kim,
Hyun Ju Han,
Yukyung Choi,
Arum Choi,
Joohyuk Sohn,
Seung Il Kim
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0225082
Subject(s) - olaparib , carboplatin , breast cancer , triple negative breast cancer , brca mutation , medicine , oncology , cancer research , cancer , chemotherapy , ovarian cancer , biology , cisplatin , genetics , poly adp ribose polymerase , polymerase , gene
Purpose A patient-derived xenograft (PDX) model is an in vivo animal model which provides biological and genomic profiles similar to a primary tumor. The characterization of factors that influence the establishment of PDX is crucial. Furthermore, PDX models can provide a platform for chemosensitivity tests to evaluate the effectiveness of a target agent before applying it in clinical trials. Methods We implanted 83 cases of breast cancer into NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic mice, to develop PDX models. Clinicopathological factors of primary tumors were reviewed to identify the factors affecting engraftment success rates. After the establishment of PDX models, we performed olaparib and carboplatin chemosensitivity tests. We used PDX models from triple-negative breast cancer (TNBC) with neoadjuvant chemotherapy and/or germline BRCA1 mutations in chemosensitivity tests. Results The univariate analyses (p<0.05) showed factors which were significantly associated with successful engraftment of PDX models include poor histologic grade, presence of BRCA mutation, aggressive diseases, and death. Factors which were independently associated with successful engraftment of PDX models on multivariate analyses include poor histologic grade and aggressive diseases status. In chemosensitivity tests, a PDX model with the BRCA1 L1780P mutation showed partial response to olaparib and complete response to carboplatin. Conclusions Successful engraftment of PDX models was significantly associated with aggressive diseases. Patients who have aggressive diseases status, large tumors, and poor histologic grade are ideal candidates for developing successful PDX models. Chemosensitivity tests using the PDX models provide additional information about alternative treatment strategies for residual TNBC after neoadjuvant chemotherapy.