Inflammatory breast cancer (IBC) is the most lethal and aggressive form of breast cancer; it is highly likely to spread to other sites in the body. There is an urgent need to establish novel treatment strategies to reduce IBC recurrence and metastasis. The aim of this work is to provide a comprehensive overview of signaling pathways in IBC, covering understanding of their function in IBC tumor cells and cells surrounding tumor, and clinical efforts to target these pathways for patients with IBC. The findings described in this work will help guide the development of effective therapies through preclinical and clinical research, eventually improving the treatment of patients with IBC.

Inflammatory breast cancer (IBC), although rare, is the most aggressive type of breast cancer. Only 2–4% of breast cancer cases are classified as IBC, but—owing to its high rate of metastasis and poor prognosis—8% to 10% of breast cancer-related mortality occur in patients with IBC. Currently, IBC-specific targeted therapies are not available, and there is a critical need for novel therapies derived via understanding novel targets. In this review, we summarize the biological functions of critical signaling pathways in the progression of IBC and the preclinical and clinical studies of targeting these pathways in IBC. We also discuss studies of crosstalk between several signaling pathways and the IBC tumor microenvironment.