Exercise to Mitigate Premature Vascular Aging After Doxorubicin Breast Cancer Therapy

Abstract

Breast cancer treatment induces a state of premature vascular aging. This article examines the hypothesis that high-intensity interval training may be a time-efficient form of exercise training that effectively mitigates premature vascular aging in breast cancer survivors.

Keywords: adjuvant breast cancer therapy; breast cancer; chemotherapy; exercise; oxidative stress; vascular aging.

Figure 1.

Working hypothesis of breast cancer chemotherapy-induced premature vascular aging: mitigation by high-intensity interval training. Proposed model illustrating the potential protective effects of high-intensity interval training (HIIT) as an exercise preconditioning strategy against chemotherapy-induced premature vascular aging. Chemotherapy contributes to vascular dysfunction through endothelial dysfunction, arterial stiffening, reduced nitric oxide (NO) bioavailability, increased reactive oxygen species (ROS) bioactivity and inflammation, elastin fragmentation, and collagen deposition. These mechanisms collectively accelerate vascular aging and elevate cardiovascular risk. Implementing a time-efficient form of exercise training, such as HIIT, between breast cancer diagnosis and the onset of chemotherapy treatment (~3 wk) may help mitigate these effects, potentially improving vascular resilience and reducing cardiovascular complications in patients with breast cancer.

Figure 2.

Premature vascular aging induced by administration of doxorubicin (Doxo) chemotherapy. Doxo administration in young adult mice induces premature vascular aging as evidenced by (A) reduced carotid artery endothelium-dependent dilation to increasing doses of acetylcholine (ACh) and (B) elevated aortic pulse wave velocity. *P < 0.05 vs Young Control. [Panel A adapted from Clayton et al. (53). Copyright © 2020 The Authors. CC BY-NC-ND. Used with permission.] [Panel B adapted from Clayton et al. (54). Copyright © 2021 American Heart Association. Used with permission.]

Figure 3.

Conceptual model depicting key factors influencing premature vascular aging in breast cancer. Central to the figure is the relation between breast cancer and vascular aging, with contributing factors including the type of exercise training, chronological age, menopausal status, breast cancer type, which informs the type of treatment, and social factors. Different breast cancer subtypes, such as invasive ductal carcinoma, inflammatory breast cancer, and invasive lobular carcinoma, may have distinct impacts on vascular health. Social determinants of health, including socioeconomic status, healthcare access, social network, and psychosocial stress, can further influence outcomes. In contrast, resistance training may serve as a protective factor by improving vascular function and mitigating premature aging effects.