A retrospective analysis of 9,524 patients enrolled in 10 adjuvant trials, led by the International Breast Cancer Study Group in the pre-trastuzumab era, reported that the 10-year cumulative incidence of brain as primary site of metastasis was 2.7% in patients with HER2-positive tumors and 1.0% in patients with HER2-negative tumors (p<0.01) [56]. The gene discussed is ERBB2; the disease is breast cancer.