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Establishment of Chemosensitivity Tests in Triple-Negative and BRCA-mutated Breast Cancer Patient-Derived Xenograft Models

 Hyung Seok Park  ;  Jeong Dong Lee  ;  Jee Ye Kim  ;  Seho Park  ;  Joo Heung Kim  ;  Hyun Ju Han  ;  Yeon A Choi  ;  Ae Ran Choi  ;  Joo Hyuk Sohn  ;  Seung Il Kim 
 PLOS ONE, Vol.14(12) : e0225082, 2019-12 
Journal Title
Issue Date
Animals ; Antineoplastic Agents / therapeutic use* ; BRCA1 Protein / genetics* ; Carboplatin / therapeutic use* ; Disease Models, Animal ; Female ; Humans ; Mice ; Mice, Inbred NOD ; Neoadjuvant Therapy ; Phthalazines / therapeutic use* ; Piperazines / therapeutic use* ; Treatment Outcome ; Triple Negative Breast Neoplasms / drug therapy* ; Triple Negative Breast Neoplasms / genetics ; Triple Negative Breast Neoplasms / pathology ; Xenograft Model Antitumor Assays*
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.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Il(김승일)
Kim, Joo Heung(김주흥) ORCID logo https://orcid.org/0000-0002-0417-8434
Kim, Jee Ye(김지예) ORCID logo https://orcid.org/0000-0003-3936-4410
Park, Se Ho(박세호) ORCID logo https://orcid.org/0000-0001-8089-2755
Park, Hyung Seok(박형석) ORCID logo https://orcid.org/0000-0001-5322-6036
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
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