Li Jian, Luo Hui, Liu Ying-Ying, Chen Li-Xin, Zhu Mei-Qin, Deng Quan-Tong, Zhu Dong-Mei, Wang Zi-Mo, Xu Jin-Feng
Department 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.
Department 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.
Pharmgenomics Pers Med. 2022 Mar 15;15:215-225. doi: 10.2147/PGPM.S351718. eCollection 2022.
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.
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.
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.
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.
探讨尿苷二磷酸葡萄糖醛酸基转移酶2B7（UGT2B7）-161单核苷酸多态性对接受帕妥珠单抗联合曲妥珠单抗治疗的中国人类表皮生长因子2（HER-2）阳性乳腺癌患者心脏毒性发生的预测价值。
本研究纳入50例计划接受曲妥珠单抗和帕妥珠单抗治疗超过4个周期的HER-2阳性乳腺癌患者，并采集血样。选取30名年龄匹配的健康志愿者作为对照组。在治疗前（M0）和治疗第3个月的4个周期结束时（M3）测量整体做功指数、整体有效做功和整体无效做功等心肌参数。在M0阶段采集患者血样，检测UGT2B7-161基因的多态性，以评估不同基因表型对心肌药物毒性损伤的预测能力。
50例患者中有35例出现心肌做功下降事件。携带UGT2B7-161 CC、CT和TT基因型的患者分别有24例（47.3%）、15例（40.8%）和11例（11.8%）。与CC基因型（41.7%）相比，UGT2B7-161 TT和CT基因型中心肌做功下降的发生率降低（12.5%），差异有统计学意义（P<0.001）。多因素logistic回归模型分析显示，UGT2B7-161基因型、体重指数和心肌肌钙蛋白I是影响心脏毒性风险的独立因素。
UGT2B7-161单核苷酸多态性是接受曲妥珠单抗和帕妥珠单抗双靶向药物治疗的HER-2阳性乳腺癌患者心脏毒性的潜在预测因素。
