Thromboinflammatory pathways in breast cancer: clinical and molecular insights into venous thromboembolism risk - a narrative review.

Abstract

Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality in breast cancer patients, particularly in those with advanced disease or undergoing systemic therapies. While breast cancer is not traditionally classified among the most thrombogenic malignancies, accumulating evidence suggests that tumor biology, treatment modalities, and systemic inflammation can collectively heighten thrombotic risk. This has led to a growing interest in the concept of thromboinflammation, wherein the coagulation cascade and inflammatory responses are intricately linked, creating a prothrombotic and tumor-supportive environment. At the molecular level, breast cancer cells and associated stromal elements contribute to a hypercoagulable state through increased expression of tissue factor (TF), release of pro-inflammatory cytokines, and production of TF-bearing extracellular vesicles. Furthermore, components of the innate immune system, particularly neutrophils, promote thrombosis via the formation of neutrophil extracellular traps (NETs). These mechanisms not only facilitate clot formation but also enhance cancer progression, metastasis, and resistance to therapy. Certain aggressive breast cancer subtypes, including triple-negative and HER2-positive tumors, demonstrate heightened thromboinflammatory activity.