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Background  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.    Objectives  This study evaluated the presence of associations between  CBR3  V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment.    Methods  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 0 month ) and at 6 months (t 6 months ) 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).    Results  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.    Conclusions   CBR3  V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.    Supplementary Information  The online version contains supplementary material available at 10.1186/s40959-021-00103-0.

CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin