Progesterone and Breast Cancer: an NCI Workshop Report

[...]the NCI workshop focused on addressing the role P4/PR plays in regulating multiple signaling pathways and the context in which PR acts to inhibit tumor growth versus its ability to drive tumor heterogeneity and stem cell growth. The ER/PR interaction with c-Src kinase and hormone-dependent activation of downstream MAPKs was first defined by seminal studies in 1998 (4) and a role for ER/PR transcriptional complexes in the regulation of global gene expression was later demonstrated by gene profiling and RIME studies performed in breast cancer models (2, 3, 5). [...]uncertainty may arise in staining of samples that are not fixed and processed in the same way as human tissues handled in a routine clinical pathology setting (e.g., cells fixed on slides, mouse tissues, fixed but not processed in the same way). [...]it is true that a subset of PR monoclonal antibodies recognizes only the PR-A isoform in archival FFPE tissue (14). LOH of the PGR gene locus occurs with high frequency in breast cancer, as does loss of ER (23). [...]while approximately 70% of newly diagnosed luminal type breast tumors are ER+/PR+, about 40% and 25% of these tumors exhibit loss of heterozygosity (LOH) at either the PGR or ESR1 gene locus, respectively (5); ER and PR LOH are positively correlated.