Patel TA, Ensor JE, Creamer SL, et al. - Given the efficacy of neoadjuvant dual human epidermal growth factor receptor (HER2) blockade with trastuzumab and pertuzumab plus paclitaxel in achieving an overall pathologic complete response rate of 46% and the efficacy of HER2 blockade with ado-trastuzumab emtansine (T-DM1) and lapatinib plus nab-paclitaxel in patients with metastatic HER2-positive breast cancer, researchers sought to test neoadjuvant effectiveness of this regimen. In this open-label, multicenter, randomized, phase II trial patients were randomized (in the experimental arm) to receive either 6 weeks of targeted therapies (T-DM1 and lapatinib) followed by T-DM1 every 3 weeks, lapatinib daily, and nab-paclitaxel weekly for 12 weeks or to receive (in the standard arm) 6 weeks of trastuzumab and pertuzumab followed by trastuzumab weekly, pertuzumab every 3 weeks, and paclitaxel weekly for 12 weeks. Outcomes revealed higher efficacy of the neoadjuvant treatment with T-DM1, lapatinib, and nab-paclitaxel vs the standard treatment in early-stage HER2-positive breast cancer. This was particularly observed in the estrogen receptor-positive cohort.