Potential role of CMPK1 , SLC29A1 , and TLE4 polymorphisms in gemcitabine-based chemotherapy in HER2-negative metastatic breast cancer patients: pharmacogenetic study results from the prospective randomized phase II study of eribulin plus gemcitabine versus paclitaxel plus gemcitabine (KCSG-BR-13-11)

ESMO Open

article

E.H. Cho¹  J.-Y. Kim²  S.-A. Im³  K.H. Jung⁴  J. Sohn⁵  K.S. Lee⁶  Y.S. Chae⁷  K.H. Lee⁸  J.H. Kim⁹  J.-H. Jang^1,10  J.H. Ahn^1,11  M.S. Park^1,12  S.-Y. Lee^1,10  Y.H. Park² 

[1] Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine;Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine;Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, College of Medicine, Seoul National University;Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine;Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine;Center for Breast Cancer, National Cancer Center;Department of Internal Medicine, Kyungpook National University Hospital;Department of Internal Medicine, Chungbuk National University Hospital;Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine;Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine;Biomedical Statistics Center, Data Science Research Institute, Samsung Medical Center;Department of Statistics, Keimyung University;Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center;Department of Health Science and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University;Director of International Cooperation Committee, Korean Society of Medical Oncology

关键词: gemcitabine;    breast cancer;    genetic polymorphism;    pharmacogenetics;   

DOI  :  10.1016/j.esmoop.2021.100236

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients.Patients and methods This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed.Results A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001).Conclusions Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.

【 授权许可】

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