Pre-Clinical and Clinical Studies of Breast Cancer prevention with Tranddermal Anti-Progesterone Agents

We continue to investigate the role of the progesterone pathway in breast cancer causation and prevention (and potentially also in treatment). Over the past few years, with BCRF support, we have studied new (safer) anti-progesterone agents in breast cancer prevention models, with encouraging results. In the past year, we have extended these studies to the prevention of breast cancer related to BRCA gene mutations, initially using a mouse model. We find that the anti-progesterone drug telapristone decreases (but does not completely prevent) tumor formation in this model. Other complete blockers of progesterone may be more effective, and we are planning experiments with these. We will then take the insights gained from the mouse model to human breast samples from BRCA1 mutation carriers, to see if similar gene signals operate in human samples, that may allow us to predict in the future whether an anti-progesterone strategy will work in a particular woman. In parallel, information gained from our BCRF-funded clinical trial of telapristone in women without BRCA mutations will further guide and inform the best use of this group of drugs in women with breast cancer and those at risk for it.