As reviewed below, we show that 40–50% of breast cancer patients, including a most aggressive subset of patients identified as ER-/PR-/HER-2- or “triple-negative breast cancer (TNBC)” reveal an upregulation of the inflammation-associated enzyme cyclooxygenase (COX)-2, which drives tumor progression and metastasis, and that prostaglandin E receptor EP4, a GPCR family member, presents as a promising newer therapeutic target in these patients. Here, ERBB2 is linked to breast cancer.