Role for mifepristone in breast cancer

Abstract

Mifepristone (MFP) is an antiprogestin that has shown some beneficial effects in breast cancer clinical trials. Interestingly, progestins such as medroxyprogesterone acetate (MPA) have also been used as second or third line therapies for breast cancer patients. The mechanisms behind the inhibitory or stimulatory actions of progestins/antiprogestins in breast cancer are still not well understood. We have shown that MFP induces the regression of murine mammary carcinomas with higher ratios of progesterone receptor isoform A (PR-A) vs. isoform B (PR-B) expression. We have also demonstrated that the stimulatory effect of progesterone or the inhibitory effects of MFP on tumor progression are achieved even in tumors transplanted in animals constitutively lacking expression of the PR (PRKO mice), and in immune-compromised mice, thus ruling out possible indirect systemic effects. The fact that the expression of PR isoforms may be directly implicated in the MFP-mediated responses in breast cancer, emphasizes the relevance of understanding the role of PR modulating malignant cell growth, and underscores the significance of evaluating PR isoforms in breast cancer samples to determine their susceptibility to MFP treatment.