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).

E H Cho, J-Y Kim, S-A Im, K H Jung, J Sohn, K S Lee, Y S Chae, K H Lee, J H Kim, J-H Jang, J H Ahn, M S Park, S-Y Lee, Y H Park

Journal: ESMO open 2021;6(5):100236

PMID: 34438242

Free Full Text on Elsevier Science View on PubMed

Abstract

[{"label":"BACKGROUND","text":"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."},{"label":"PATIENTS AND METHODS","text":"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."},{"label":"RESULTS","text":"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\u00a0= 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\u00a0= 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)."},{"label":"CONCLUSIONS","text":"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."},{"copyright":"Copyright \u00a9 2021 The Authors. Published by Elsevier Ltd.. All rights reserved."}]

Address: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.; Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, College of Medicine, Seoul National University, Seoul, South Korea.; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.; Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.; Center for Breast Cancer, National Cancer Center, Goyang, South Korea.; Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea.; Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea.; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.; Biomedical Statistics Center, Data Science Research Institute, Samsung Medical Center, Seoul, South Korea.; Department of Statistics, Keimyung University, Daegu, South Korea.; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Seoul, South Korea; Department of Health Science and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, South Korea. Electronic address: [email protected].; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Director of International Cooperation Committee, Korean Society of Medical Oncology, Seoul, South Korea. Electronic address: [email protected].

DOI: 10.1016/j.esmoop.2021.100236