No studies investigated the association of with cardiotoxicity of treatment with RT or trastuzumab

On By msisig

No studies investigated the association of with cardiotoxicity of treatment with RT or trastuzumab. genotyping of rs854560 and rs662, rs1138272 and rs1695, rs4880, rs1001179, and rs1154965 polymorphisms. N-terminal pro B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction, and NYHA class were used as markers of cardiotoxicity. We used logistic regression to evaluate the association of genetic factors with markers of cardiotoxicity. Results Carriers of at least one polymorphic rs854560 allele were less likely to have increased NT-proBNP (OR = 0.34; 95% CI?=?0.15-0.79; = 0.012), even after adjustment for age (OR = 0.35; 95% CI?=?0.15-0.83; = 0.017). Carriers of at least one polymorphic rs662 allele were more likely to have increased NT-proBNP (OR = 4.44; 95% CI?=?1.85-10.66; = 0.001), even after adjustment Rabbit Polyclonal to p53 for age (OR = 5.41; 95% CI?=?2.12-13.78; 0.001). rs1695 was also associated with decreased NT-proBNP in the multivariable analysis (= 0.026), while rs1001179 was associated with NYHA class in the univariable (= 0.012) and multivariable analysis (= 0.023). Conclusion In our study, polymorphisms rs662 and rs854560, rs1001179, VCH-916 and rs1695 VCH-916 were significantly associated with the occurrence of cardiac adverse events after adjuvant RT and could serve as biomarkers contributing to treatment personalization. 1. Introduction Adjuvant radiotherapy (RT) has significantly improved disease-specific survival for patients with early-stage breast cancer [1, 2]. As a consequence, more cancer survivors may experience late complications of treatment [3]. Radiation dose received by the heart during adjuvant RT of breast or thoracic wall may result in a range of cardiotoxic effects including coronary artery disease, cardiomyopathy, pericardial disease, valvular dysfunction, and conduction abnormalities [4, 5]. There is no minimum radiation dose to the heart that is entirely safe [4]. A combination of adjuvant RT and systemic oncological treatment may have an even worse impact on the cardiac-related outcome [6]. This combination is frequently used in HER2-positive breast cancer, a subtype of breast cancer with amplification or overexpression of the human epidermal growth factor receptor 2 (HER2) oncogene, which represents approximately 15% of all breast cancers [7, 8]. In standard clinical practice, this subtype of breast cancer is usually treated with a least two types of cardiotoxic systemic treatment [7, 9]. Anthracyclines are prescribed as a VCH-916 part of neoadjuvant or adjuvant chemotherapy and are followed by anti-HER2 treatment with trastuzumab, a monoclonal antibody [9]. Both types of treatment increase the survival of HER2-positive breast cancer patients but are cardiotoxic [10C13]. Anthracycline-related cardiotoxicity results, at least to some degree, in myocyte destruction and clinical heart failure and is irreversible. Trastuzumab-related cardiotoxicity is usually most often manifested by an asymptomatic decrease in left ventricular ejection fraction (LVEF) and less often by clinical heart failure [13C15]. Different biomarkers and imaging techniques and their potential role in monitoring cardiotoxicity have already been evaluated [6]. The use of blood-based biomarkers to detect radiation or systemic treatment-induced cardiotoxicity is very promising as it is usually minimally invasive, affordable, and repeatable [16]. Currently, the determination of LVEF and N-terminal pro-brain natriuretic peptide (NT-proBNP) is mostly used for monitoring cardiotoxicity of cancer treatment [14, 17, 18]. LVEF is the golden standard for monitoring cardiac function in patients receiving cardiotoxic therapy. Echocardiography and radionuclide ventriculography are imaging techniques that are being most widely used in this setting for the assessment of LVEF [14]. Brain natriuretic peptide (BNP), a member of the family of natriuretic hormones, seems to be one of the most appropriate biomarkers for cardiotoxicity evaluation [19, 20]. After being synthesized, its inactive form is usually then cleaved into active BNP and inactive NT-proBNP. NT-proBNP is usually a sensitive biomarker of both systolic and diastolic heart failure [21]. NT-proBNP was also an early and sensitive diagnostic and prognostic biomarker for the evaluation of cardiotoxicity of cancer chemotherapy and RT [20, 22, 23]. Patients with elevated NT-proBNP had a higher possibility of asymptomatic LVEF reduction or developing symptomatic heart failure later on. Because changes in NT-proBNP usually occur earlier than changes in LVEF, its elevated level exposes patients at higher risk. One of the molecular mechanisms associated with cancer treatment response and occurrence of.