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; and the related drug ulipristal acetate (UPA) does the same in a mouse model with a defective BRCA1 gene. These are exciting results, and we are building on them by testing the combination of UPA with an active metabolite of tamoxifen, called endoxifen. At present, we are doing this in a mouse model, and expect results on this combination by the end of the present funding cycle. For the next cycle, we propose to study the tumors and the mammary glands of these mice to identify gene pathways that are associated with successful prevention of breast cancer. Among mice that develop tumors despite therapy, we will look for predictors of prevention failure. We hope that our data will lead to clinical trials of UPA+endoxifen for breast cancer prevention and for therapy that will improve upon the encouraging results seen in our clinical trial of telapristone (the manuscript is under review). In the telapristone clinical trial, we have identified exciting connections of progesterone signaling with other pathways that point to additional opportunities and new directions for testing in clinical trials.
|Effective start/end date||10/1/19 → 9/30/20|
- Breast Cancer Research Foundation (BCRF-19-087)
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