HFE Gene Variants' Impact on Anthracycline-Based Chemotherapy-Induced Subclinical Cardiotoxicity.

Progress in oncology has allowed to improve outcomes in many breast cancer patients. The core stone of breast cancer chemotherapy is anthracycline-based chemotherapy. Unfortunately, anthracyclines cause cardiotoxicity which is a limiting factor of its use and lifetime cumulative dose of anthracyclines is the major risk factor for cardiotoxicity. With evolution of echocardiography subclinical damage is identified, and more sensitive evaluation can be performed. This leads to understanding the heart damage beyond cumulative dose in early phase and importance of other risk factors. There are many risk factors for anthracycline-based chemotherapy cardiotoxicity (ABCC) like arterial hypertension, obesity, diabetes, genetic predisposition, etc. One of possible pathophysiological pathways is iron metabolism, especially HFE gene-regulated iron metabolism pathway. Pre-existing genetic iron metabolism dysregulation increases risk for ABCC. Clinical studies and experimental models in mice have shown potential impact of HFE gene SNP on ABCC. The main objective of our study was to identify the impact of HFE C282Y and H63D SNP on the development of subclinical heart damage during and/or after doxorubicin-based chemotherapy in breast cancer patients. Data of 81 women with breast cancer treated with doxorubicin-based chemotherapy in the outpatient clinic were analyzed and SNP RT-PCR tests were performed. Statistically significant association between H63D and ABCC after completion of chemotherapy was observed (p < 0.005). Consequently, our study demonstrated that H63D SNP has an important role in the development of ABCC. HFE SNP mutation status could be used as one of important tools to identify high-risk patients for ABCC.

Impact of Arterial Hypertension on Doxorubicin-Based Chemotherapy-Induced Subclinical Cardiac Damage in Breast Cancer Patients.

Advances in oncologic therapies have allowed to achieve better outcomes and longer survival in many patients with breast cancer. Anthracyclines are cytotoxic antibiotics widely used in daily oncology practice. However, anthracyclines cause cardiotoxicity which is a limiting factor of its use. Cumulative dose of anthracyclines is the major cause of induced cardiotoxicity. According to previous clinical trials, the major predisposing high-risk factors for anthracycline-based chemotherapy-induced cardiotoxicity are age, body weight, female gender, radiotherapy, and other diseases such as diabetes and hypertension. Experimental studies in animals confirm that hypertension may be a significant factor predisposing anthracycline-based chemotherapy cardiotoxicity. The main objective of our study was to identify the effect of pre-existing arterial hypertension on the development of subclinical cardiac damage during or after doxorubicin-based chemotherapy in breast cancer patients. The study was performed prospectively between March 2016 and January 2017 in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics Department of Oncology and Department of Cardiology. Data of 73 women with breast cancer treated with doxorubicin-based chemotherapy in outpatient clinic were analyzed. Statistically significant association between pre-existing arterial hypertension and left ventricular systolic dysfunction after completion of chemotherapy was observed (P < 0.004). Our study demonstrated that pre-existing arterial hypertension has a very important role in the development of anthracycline-based chemotherapy-induced cardiotoxicity, despite arterial hypertension control quality. Consequently, further studies evaluating impact of other risk factors and how early and sufficient management of arterial hypertension could influence the development of cardiotoxicity are needed to avoid permanent cardiac damage.