In this heightened signaling context, we predict that a subset of ER+ luminal breast tumor cells that appear to be PR-low (or PR-null) by standard clinical protein immunohistochemistry (IHC) assays may in fact express short-lived phospho-PR species that are SUMO-deficient and thus transcriptionally hyperactive at phospho-PR target genes important for breast cancer cell proliferation and pro-survival. The gene discussed is ESR1; the disease is breast carcinoma.