Sympathetic Overdrive, Vascular Dysfunction, and Exercise Intolerance in Long-Term Breast Cancer

Journal of the American Heart Association, Volume 15, Issue 6 , March 17, 2026. BackgroundLong‐term survivors of breast cancer (BC) treated with doxorubicin and trastuzumab‐based chemotherapy are at increased risk of developing cardiovascular disease.

However, the physiological mechanisms associated with increased cardiovascular disease risk are completely unknown. We hypothesized that long‐term survivors of BC, compared with controls, exhibit sympathetic neural hyperactivity, vascular dysfunction, cardiac morphofunctional changes, exercise intolerance, and alterations in the circulating milieu.MethodsTwenty‐three survivors of BC (age: 48.9±1.3 years; body mass index: 25.2±0.8 kg/m2) and 18 (age: 46.4±1.3 years; body mass index: 26.8±0.8 kg/m2) well‐matched controls were studied.

Muscle sympathetic nerve activity (microneurography), brachial artery flow‐mediated dilation (ultrasound‐Doppler), carotid‐femoral pulse wave velocity (tonometry), left ventricular ejection fraction and global longitudinal strain (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), endothelial cell‐derived extracellular vesicles (flow cytometry), and plasma metabolome (mass spectrometry) were assessed. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects.ResultsSurvivors of breast cancer were tested ⁓8 years after cancer treatment completion.