Lang Jennifer K, Karthikeyan Badri, Quiñones-Lombraña Adolfo, Blair Rachael Hageman, Early Amy P, Levine Ellis G, Sharma Umesh C, Blanco Javier G, O'Connor Tracey
Department of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, 14203, USA.
Veterans Affairs Western New York Healthcare System, Buffalo, NY, USA.
Cardiooncology. 2021 May 11;7(1):17. doi: 10.1186/s40959-021-00103-0.
The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts.
This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment.
We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t) and at 6 months (t) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson's biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA).
Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups.
CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.
CBR3 V244M单核苷酸多态性与儿童癌症幸存者中蒽环类药物相关心肌病的风险有关。关于CBR3 V244M对成年人群蒽环类药物相关心脏毒性风险影响的前瞻性研究有限。
本研究评估了接受多柔比星治疗的乳腺癌患者中CBR3 V244M基因型状态与超声心动图参数变化之间的关联。
我们招募了155例在罗斯韦尔公园综合癌症中心（纽约州布法罗）接受多柔比星（DOX）治疗的乳腺癌患者，进行一项前瞻性单臂观察性药物遗传学研究。对患者进行CBR3 V244M变异的基因分型。92例患者在基线（t）以及DOX治疗后6个月（t）进行了超声心动图检查。由对所有患者数据不知情的研究人员使用辛普森双平面法则，通过心尖两腔和四腔超声心动图图像计算容积和左心室射血分数（LVEF）。通过将心脏容积除以体表面积（BSA）对容积指数进行评估。
与DOX治疗前的基线研究相比，CBR3 GG和AG基因型的乳腺癌患者在开始DOX治疗乳腺癌6个月后LVEF均出现了统计学上的显著降低。与杂合AG基因型患者相比，CBR3 V244M G等位基因纯合子（CBR3 V244）患者在DOX治疗6个月后LVEF进一步出现了统计学上的显著降低。我们发现CBR3基因型组之间在年龄、与心肌损伤相关的既往心脏病、累积DOX剂量或心脏保护药物的同时使用方面没有差异。
CBR3 V244M基因型状态与接受乳腺癌化疗的受试者中提示早期蒽环类药物相关心肌病的超声心动图参数变化有关。
