Value of UGT2B7-161 Single Nucleotide Polymorphism in Predicting the Risk of Cardiotoxicity in HER-2 Positive Breast Cancer Patients Who Underwent Pertuzumab Combined with Trastuzumab Therapy by PSL

Abstract

Jian Li,1,* Hui Luo,1,* Ying-Ying Liu,1 Li-Xin Chen,1 Mei-Qin Zhu,2 Quan-Tong Deng,2 Dong-Mei Zhu,1,3 Zi-Mo Wang,1 Jin-Feng Xu1 1Department of Ultrasound, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, People’s Republic of China; 2Department of Medical Oncology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, People’s Republic of China; 3Department of Ultrasound, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Li; Jin-Feng Xu, Department of Ultrasound, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), No. 1077 of Dongmenbei Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]; [email protected]: To explore the value of uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7)-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in Chinese human epidermal growth factor 2 (HER-2) positive breast cancer patients who underwent pertuzumab combined with trastuzumab Therapy.Methods: Fifty patients with HER-2 positive breast cancer who planned to receive trastuzumab and pertuzumab therapy for more than four cycles were enrolled in this study, and blood samples were collected. Thirty healthy volunteers of matching ages were selected as the control group. Myocardial parameters such as global work index, global effective work, and global wasted work were measured before treatment (M0) and at the end of four cycles of treatment month three (M3). Blood samples were collected from patients at the M0 stage, and polymorphisms of the UGT2B7-161 gene were detected to evaluate the predictive ability of different gene phenotypes on the myocardial drug toxicity injury.Results: There were 35 myocardial work decreased events among 50 patients. There were 24 (47.3%), 15 (40.8%), and 11 (11.8%) patients carrying UGT2B7-161 CC, CT, and TT genotypes, respectively. The occurrence of myocardial work decreased was decreased in UGT2B7-161 TT and CT genotypes (12.5%) compared with CC genotype (41.7%) with statistical significance (P < 0.001). Multivariate logistic regression model analysis exhibited that UGT2B7-161 genotypes, body mass index, and cardiac troponin I were independent factors influencing the risk of cardiotoxicity.Conclusion: UGT2B7-161 single nucleotide polymorphism is a potential predictive factor for cardiotoxicity in HER-2 positive breast cancer patients receiving trastuzumab and pertuzumab dual-targeted drug therapy.Keywords: breast cancer, uridine diphosphate-glucuronosyltransferase 2B7, pressure-strain loop, human epidermal growth factor 2, cardiotoxicity, trastuzumab, pertuzumab

Keywords

• breast cancer
• uridine diphosphate-glucuronosyltransferase 2b7
• pressure-strain loop
• human epidermal growth factor 2
• cardiotoxicity
• trastuzumab
• pertuzumab