Massachusetts General Hospital Boston United States
Making a major impact on the incidence and lethality of breast cancer will require a detailed understanding of the earliest tissue changes that ultimately drive the process of breast cancer development. There is no substitute for the ability to define and understand the early, pre-malignant changes as they occur in women who are breast cancer-predisposed. One group of women at high breast cancer risk up to 80 lifetime breast cancer risk are those who have inherited mutations in the BRCA1 and BRCA2 genes. Currently, the only way these women can eliminate their risk is to undergo bilateral mastectomy before developing cancer. We have established an IRB-approved protocol that allows us to collect and analyze a portion of this tissue. Here, we propose detailed functional and molecular analysis of these tissues in order to reveal critical early steps in breast cancer development. We will then test how reversing these changes can prevent breast cancer in well-established animal models. These studies are likely to lead directly to clinical trials of new approaches to prevent breast cancer.