Preclinical and Clinical Studies of Breast Cancer Prevention with Transdermal 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. We find that the anti-progesterone drug telapristone decreases tumor formation in a rat model; we have completed an early phase trial of telapristone in women with Stage I-II breast cancer; and have started a second trial to see if this can be delivered through the breast skin, rather than by mouth, thus reducing risk of side effects. We have completed examination of samples from our clinical trial to identify predictors of benefit from telapristone therapy (we will report the results shortly), and expect that these results will allow us to design future larger trials can be tailored to the right women and the right tumors. We are also hopeful that this approach can be used successfully for breast cancer prevention in BRCA gene carriers, and we are continuing to test anti-progesterone agents in laboratory models in preparation for a trial in this group of women. In addition combined inhibition of anti-progesterone and anti-estrogen drugs may allow lower doses to be used, and will likely be more effective for prevention (and possibly treatment). This is another focus of the work proposed this year.