Elía and colleagues propose that progesterone receptor (PR) ligands may serve as therapeutic tools for luminal breast cancer. Preclinical data suggest that antiprogestins inhibit tumor growth and metastasis in breast cancer models with higher levels of PR isoform A (PRA) than isoform B (PRA-H tumors), while they stimulate the metastatic burden in those with the opposite ratio. The MIPRA trial showed that mifepristone neoadjuvant treatment benefits patients with PRAH tumors and underscores the relevance of testing the PR isoform ratio before administering antiprogestins to patients with breast cancer. Proteomics, coupled with RNA-Seq profiling, revealed mifepristone-modulated biological processes that explain and strengthen the Ki67 data. The fact that lymph node metastases retain the PRA/PRB ratio as the primary tumor posits this subgroup of patients as recipients of antiprogestin treatment, even in adjuvant settings. These findings suggest that mifepristone may be included in the armamentarium against breast cancer in the future.

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