a, b, Kaplan–Meier curves for brain metastasis-free survival on the basis of BrMS status in an independent cohort of 192 breast tumours (a), and in a combined cohort of 262 breast tumours from patients who received no adjuvant therapy (b). c, Kaplan–Meier curves for brain metastasis-free survival of mice injected with the indicated cell lines expressing short hairpin RNA (shRNA) vector control or shRNA targeting COX2. d, Kaplan–Meier curves for brain metastasis-free survival of mice injected with the indicated cell lines and treated with cetuximab or vehicle control. e, Schematic of the in vitro BBB model assay system. HUVEC, human umbilical vein endothelial cells. f, In vitro BBB transmigration activity of the indicated cell lines and conditions. The number of transmigrated cells relative to the parental cell lines is plotted. Error bars, s.e.m.; n = 6–20. P values were determined by log rank test (a–d) and one-tailed unpaired t-test (f).