The estimated lifetime risk of breast cancer is increasing. Currently, 12.5% of women (1 out of 8) are expected to develop breast cancer in their lifetime, and more than 40,000 people are expected to die from breast cancer each year in the United States alone. Death from breast cancer is almost always due to metastasis. Metastasis is the spread of cancer cells from the original tumor to other parts of the body, including lymph nodes, bone, lungs, brain, and liver. While early detection and treatment are successfully reducing the incidence of advanced disease, we must tackle the problem of metastasis in order to really impact the lives of patients with breast cancer. Despite the importance and urgency of this problem, the process of metastasis is poorly understood. For example, we know that breast cancer preferentially spreads to specific organs but we do not understand why this happens. Thus, there is an immense need for improved experimental models that allow us to study the type of metastasis that is so often observed in human breast cancer.

We developed a new mouse model for breast cancer, which revealed that the product of a particular gene (MSP) promotes metastasis to many organs, but especially to the bones. Detection of high levels of MSP in human tumors was a significant, independent prognostic factor for metastasis and death. These results not only showed that MSP plays a role in metastasis, but also showed that metastasis to clinically relevant sites can be studied in mice: Development of a better model system in which to carry out testing of drugs provides an important step toward progress against breast cancer. We have established collaborations with another academic lab and several biotechnology companies to test multiple MSP pathway inhibitors that are at the preclinical stage of development. If inhibiting the MSP pathway proves effective in reducing or preventing metastasis, it will make a direct impact on breast cancer, since up to 20% of all breast cancer patients have tumors that express MSP. A positive result could warrant a clinical trial in the immediate future.

Although we have developed a sophisticated mouse model for studying metastasis and for preclinical testing of drugs, we also want to carry this one step forward: To validate the efficacy of drugs on human tumor tissue. Our goal is to transplant each of the five main human breast cancer subtypes into mice, using primary breast tumor tissue. This type of system would allow for unprecedented preclinical testing of response of each tumor subtype to combinations of existing drugs and to new drugs. This type of personalized medicine could have large potential for impact, because a patient could potentially know the best drug for their tumor, prior to undergoing therapy. Our first goal in this task is to test the MSP pathway inhibitors on human tumors that are known to express MSP.