We have shown that 1) the EGFR pathway regulates the expression of COX-2, a key molecule in the inflammatory response whose expression correlates with worse outcome of IBC patients and whose inhibition reduces IBC cells’ invasion and tumor growth; 2) both the EGFR and COX-2 pathways contribute to the regulation of IBC stemness; and 3) Nodal, a molecule involved in the regulation of stem cell pluripotency, is a key component in EGFR/COX-2-mediated CSC regulation in IBC, and both the EGFR and COX-2 pathways regulate Nodal signaling. Here, PTGS2 is linked to inflammatory breast carcinoma.