In contrast to other metastasis sites, one special challenge for breast cancer cells in arriving at the brain is to cross the BBB, which can be mitigated by multiple key molecules, such as COX2, EREG, HBEGF, ITGAV, ITGB3, ST6GALNAC5, ANGPTL4, PIEZO2, and SCNN1A [34,35,37,38,39,40]. Here, HBEGF is linked to breast cancer.