Nevertheless, a recent unplanned subgroup analysis showed a decreased cumulative incidence of BM in neratinib arm compared to placebo arm in a subset of hormone receptor positive, HER2 positive BC patients who started neratinib ≤1 year from the end of adjuvant trastuzumab28.With regards to lapatinib, ALTTO29 and NEOALTTO studies30 showed that lapatinib alone or in combination with trastuzumab in adjuvant and neoadjuvant setting did not reduce the rate of brain recurrence. This evidence concerns the gene ERBB2 and breast cancer.