The crosstalk of breast cancer and ischemic heart disease

Abstract

In recent years, the continuous optimization of anti-tumor therapy has greatly improved the cancer-specific survival rate for patients with breast cancer (BC). The prevention and treatment of breast cancer-related heart diseases have become a new breakthrough in improving the long-term survival for BC patient. The cardiac damages caused by BC treatment are increasingly prominent among BC patients, of which ischemic heart disease (IHD) is the most prominent. Besides, the systemic inflammatory response activated by tumor microenvironment c an induce and exacerbate IHD and increase the risk of myocardial infarction (MI). Conversely, IHD can also exert detrimental effects on tumors. MI not only increases the risk of BC, but also induces specialized immune cell to BC and accelerates the progression of BC. Meanwhile, the treatment of IHD can also promote BC metastasis and transition to more aggressive phenotypes. Although BC and IHD are diseases of two independent systems, their crosstalk increases the difficulty of anti-cancer treatment and IHD management, which reduces the survival for both diseases. Therefore, this review mainly explores the mutual influence and underlying mechanisms between BC and IHD, aiming to provide insights for improving the long-term survival for patients with BC or IHD.

Fig. 1. The breast cancer accelerates ischemic heart disease.

The inflammatory factors occurring in the microenvironment of breast tumor injury the vascular endothelial cells, which contributes to ischemic heart disease by inducing the formation of atherosclerosis and thrombosis. IL-1β, interleukin-1 beta；TNF-α, tumor necrosis factor-alpha；IL-6, interleukin-6；LDL, low density lipoprotein.

Fig. 2. The ischemic heart disease promotes the progression and recurrence of breast cancer.

A Cardiac interstitial stromal cells release extracellular vesicles containing specific biomolecules with reparative effects on the heart, such as osteonectin, IL-6, galectin-3, TNF-α, VEGF, etc. Extracellular vesicles enriched with these biomolecules promote tumor proliferation and migration upon reaching tumor tissue via the bloodstream [91]. B Myocardial infarction promotes the growth of transplanted breast cancer in mice; C Myocardial infarction promotes inhibitory immune cell production and aggregation in breast cancer; D Myocardial infarction promotes the growth and metastasis of spontaneous breast cancer in mice; E Cardiovascular disease accelerates breast cancer recurrence. Panels B-E were reproduced from the study by Koelwyn GJ et al, Nat Med. 2020 [92]. Copyright 2020, Springer Nature.

Fig. 3. The crosstalk between breast cancer treatment and ischemic heart disease management.

The treatment of breast cancer, such as chemotherapy and endocrine therapy and radiotherapy, lead to the ischemic heart disease by inducing the atherosclerosis and vasospasm. On the contrary, the management of ischemic heart disease, such as statins, P2Y12 inhibitor, urokinase-type plasminogen activator and vitamin B3, also promote the deterioration and metastasis of breast cancer.