Here, we report the safety and efficacy of a randomized study in patients with locally advanced, HER2+ breast cancer treated in the neoadjuvant setting with trastuzumab, neratinib, or the combination, in each case administered for 16 weeks with paclitaxel followed by standard chemotherapy with doxorubicin plus cyclophosphamide (AC) for 4 cycles. The gene discussed is ERBB2; the disease is breast cancer.