Inflammatory breast cancer (IBC) is highly aggressive and the most lethal form of locally advanced breast cancer. IBC also spreads to other body sites at a high rate. Furthermore, there is racial disparity in IBC in African Americans with an incidence rate of 10.1% compared to 6.2% for Caucasians. Inflammation, the body's response to damage caused by the breast tumor, actually works against the cancer patient by promoting the spread of the primary tumor. Understanding the mechanisms by which inflammation promotes tumor spread is the primary objective of the proposed research. One factor that plays a major role in tumor spread is a blood protein called fibrinogen. Fibrinogen helps form the blood clot needed to stop bleeding following an injury or a wound. Fibrinogen also helps to form the foundation in tissue upon which cells bind, grow, and migrate. We will test whether fibrinogen deposited at the site of the primary breast tumor promotes tumor cell migration, as well as growth of new blood vessels to help feed the tumor. A small fragment of fibrinogen has been identified that plays a key role in controlling these processes. As such, this fibrinogen fragment is an important target for therapy. By blocking the function of the fibrinogen fragment, it may be possible to block tumor cell spread and the growth of blood vessels that feed the tumor. The proposed studies will investigate how this fibrinogen fragment works, an essential first step in determining how to interfere with its function.