Overexpression of COX-2 in two poorly metastatic MCF7 (COX-2 low, human epidermal growth factor receptor 2 (HER-2) negative, progesterone receptor (PR) positive, estrogen receptor (ER) positive) and SK-BR-3 (COX-2 low, HER-2 high, ER negative) breast cancer cell lines has been shown to induce aggressive breast cancer phenotypes and promote metastasis, which could be abrogated with EP4 antagonist treatment. This evidence concerns the gene ESR1 and breast carcinoma.