Progesterone receptor isoform ratio to define the molecular signature of luminal breast cancers and their antiprogestin responsiveness.

11016 Background: Current therapies for hormone receptor (+) breast carcinomas target the estrogen receptor. Evidence indicates that the progesterone receptor (PR) also participates in cancer growth. In experimental models, we showed that mifepristone (MFP) inhibits the growth of mammary carcinomas when the predominant isoform is PR-A. The aim of our study was to confirm these observations and explore the molecular signatures of breast cancers overexpressing isoforms PR-B or PR-A. Methods: Tissue sections from 100 surgical samples were cultured with MFP (10 nM) or vehicle for 48 hs, and embedded in paraffin for Ki-67 staining. Frozen samples were processed for Western blotting (n = 360) or RNAseq (n = 16). Patients were considered PR-A(+) if PR-A/PR-B ≥ 1.2, or PR-B(+) if PR-A/PR-B ≤ 0.83. The sample size required to detect a 50% difference in MFP response between PR-A+ vs. non PR-A+ samples (type I error: 5%; type II error: 10%) was 19 patients/group. Results: MFP only inhibited Ki-67 expression in PR-A+...