The randomized, double-blind, placebo-controlled HER2CLIMB clinical trial (NCT02614794) compared a small-molecule highly selective for HER2 oral tyrosine kinase inhibitor (TKI), tucatinib, versus placebo in combination with trastuzumab and capecitabine in patients with HER2-positive metastatic BC previously treated with trastuzumab, pertuzumab, and T-DM1, which resulted in tucatinib’s approval by the FDA in 2020, also applicable for BC patients with BMs [130]. This evidence concerns the gene ERBB2 and breast cancer.