In contrast to estradiol’s generally suppressive effects on MMP-9 in vascular settings, tamoxifen (and its active metabolites, e.g., 4-hydroxytamoxifen/endoxifen) can, in a subset of ER+ breast-cancer models, promote an invasive, matrix-degradative phenotype characterized by higher MMP-9 activity. The gene discussed is MMP9; the disease is breast cancer.