The humanized mouse mammary fat pad for testing breast cancer prevention drugs

Abstract: Breast cancer prevention research requires experimental models that are relevant to the human condition. So far, these are lacking. One difficulty is that the supporting tissue (stroma) of the human breast, which plays an important part in the development and growth of the glandular tissue (and in cancer arising from the gland) is unique, and difficult to replicate in animal models. We propose to modify an existing model, developed for the study of breast cancer, to one that can be used for prevention studies. The new aspect of our proposal is that we will use fine needle biopsies obtained from mastectomy specimens (these contain both glandular and stromal cells) to establish human grafts in the mammary fat pads of mice, from which the mouse glandular tissue has been surgically removed. We anticipate that breast cancer cells and high risk normal cells will grow under these conditions, will mimic the human gland, and will allow testing experimental drugs. Specifically, we will test an anti-progesterone agent that we are also designing clinical trials for. The successful completion of these experiments will facilitate the study of preventive medications in the laboratory, and will guide the clinical trial design of promising agents.