Cardiovascular-oncogenic gene crosstalk in breast cancer: Survival, prognosis and therapeutic strategies

Table 1 Genes associated with breast cancer and cardiovascular diseases

Gene name	Role in breast cancer	Role in cardiovascular disease
JAK2	JAK2 promotes triple-negative breast cancer progression through IL-6/IL-8 signaling[29]	Promoting inflammation, blood clot formation, and vascular damage[28]
TTN	Inactivation promotes tumor progression, metastasis, immune evasion, and poor prognosis[31]	Abnormal function of this gene impairs cardiac remodeling, leading to cardiomyopathy and sudden cardiac death[30]
TET2	Low TET2 promotes aggressive breast cancer, whereas high TET2 inhibits MYC signaling, tumor growth, migration, and enhances stress-induced cell death[33]	Plays a protective role in cardiovascular disease by regulating inflammation and preventing adverse cardiac remodeling[32]
GRK4	Promotes breast cancer progression via β-arrestin-dependent mitogen-activated protein kinase signaling[35]	Regulates blood pressure via GPCR signaling[34]
AMPK	AMPK suppresses breast cancer by inhibiting PI3K/mTOR and regulating p53 signaling[40-42]	AMPK activation suppresses reactive oxygen species, oxidative stress, inflammation, and atherosclerosis-related processes[36-40]
PPAR-γ	PPAR-γ acts as a tumor-suppressive factor by limiting cellular expansion, inhibiting cellular proliferation and angiogenesis, and promoting cellular differentiation[48]	PPAR-γ activation improves endothelial function and protects against atherosclerosis[43,44]
Wnt/β-catenin	Increased β-catenin activity promotes cyclin D1-mediated proliferation, tumor progression, and aggressiveness, and is associated with poor prognosis[59]	Wnt/β-catenin dysregulation promotes endothelial dysfunction, inflammation, vascular calcification, monocyte adhesion, vascular smooth muscle cell proliferation, vascular remodeling, and neointimal formation[51-56]

JAK2: Janus kinase 2; TTN: Titin; TET2: Tet methylcytosine dioxygenase 2; GRK4: G protein-coupled receptor kinase 4; AMPK: AMP-activated protein kinase; PPAR-γ: Peroxisome proliferator-activated receptor gamma; Wnt: Wingless-related integration site; IL: Interleukin; GPCR: G protein-coupled receptor; PI3K: Phosphoinositide 3-kinase; mTOR: Mechanistic target of rapamycin; p53: Tumor protein p53.

Table 2 Cytokines associated with breast cancer and cardiovascular diseases

Cytokine	Role in breast cancer	Role in cardiovascular disease
TNF-α	TNF-α promotes breast cancer progression by enhancing tumor growth, metastasis, and inflammation, and its elevated level is associated with poor clinical outcomes[70,71]	TNF-α damages vascular endothelial cells, increasing endothelial permeability, lipid deposition, inflammation, thrombosis, and vascular smooth muscle cell proliferation, thereby promoting atherosclerosis and increasing the risk of ischemic heart disease and MI[74,75]
IL-1β	IL-1β induces IL-6 via nuclear factor kappa-light-chain-enhancer of activated B cells, promoting breast cancer progression and aggressiveness[81]	IL-1β increases endothelial adhesion molecules, promoting leukocyte recruitment and vascular inflammation. This leads to endothelial dysfunction and accelerates atherosclerosis[83,84]
IL-6	Elevated IL-6 levels correlated with unfavorable clinical outcomes in breast cancer[89]	IL-6 induces systemic inflammation and atherosclerosis, contributing to cardiovascular complications such as myocardial infarction and peripheral arterial disease[90]
TGF-β	TGF-β promotes epithelial-to-mesenchymal transition, thereby enhancing invasion, metastasis, and immune evasion, thereby supporting breast cancer progression[91,92]	Elevated TGF-β promotes cardiac fibrosis and pathological myocardial remodeling after ischemic injury, increasing the risk of ischemic heart disease and heart failure[93,94]

TNF-α: Tumor necrosis factor-alpha; IL-1β: Interleukin-1β; IL-6: Interleukin-6; TGF-β: Transforming growth factor-beta; MI: Myocardial infarction.