Abstract 17565: Sympathetic Neural Overactivity, Endothelial Dysfunction, Aortic Stiffening, and Diminished Exercise Capacity in Breast Cancer Survivors Treated With Doxorubicin and Trastuzumab-Based Chemotherapy

Abstract

Introduction: Previous evidence demonstrates that breast cancer (BC) survivors who were treated with doxorubicin and trastuzumab-based chemotherapy have an increased risk of developing cardiovascular (CV) disease at least 7 years after completion of cancer treatment. The reasons for the increased CV disease risk are not completely understood, a constellation of physiological changes may contribute. We hypothesized that BC survivors compared with age- and body mass index (BMI), sex -matched healthy controls, exhibit sympathetic neural overactivity, vascular endothelial dysfunction, aortic stiffening, and diminished exercise capacity. Methods: Twelve women BC survivors, treated with doxorubicin and trastuzumab (age=48±2 years and BMI=28±2 Kg/m 2 ) and fourteen women control subjects (age=46±1 years and BMI=27±1 Kg/m 2 ) were studied. Muscle sympathetic nerve activity (MSNA, Microneurography), endothelium-dependent dilation (brachial artery flow-mediated dilation, BAFMD), aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), blood pressure (BP, Finometer), heart rate (HR, Electrocardiogram), and peak oxygen uptake (V˙O 2 peak, Cardiopulmonary exercise testing) were measured. Results: BC survivors were evaluated 8±2 years after the completion of cancer treatment. Burst frequency and burst incidence of MSNA were higher and BAFMD and V˙O 2 peak were lower in BC survivors than in controls ( p <0.001). There were not differences between the groups in CFPWV, BP, and HR ( p >0.05). MSNA burst frequency and burst incidence were inversely associated with V˙O 2 peak or BAFMD ( p <0.05). Conclusion: Our findings demonstrate that BC survivors have an augmented sympathetic neural activity, endothelial dysfunction, and attenuated exercise capacity, which may help to explain, at least in part, the increased CV risk in this population. Therefore, it is urgent to establish therapeutic strategies (e.g., physical exercise rehabilitation) to restore or alleviate these cardiovascular changes in BC survivors.