Abstract

The addition of trastuzumab to chemotherapy dramatically improved the prognosis of early-stage human epidermal growth factor receptor 2 (HER2)–positive breast cancer. However, 15%-31% of patients still develop disease recurrence, on the basis of long-term follow-up of adjuvant pivotal trials. A better understanding of tumor biology has led to the development of optimized anti-HER2 drugs and add-on strategies to further improve survival outcomes. In the neoadjuvant setting, dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy has increased the rate of pathologic complete response, a surrogate marker of improved longterm outcome; yet, in the adjuvant setting, it has led to small benefits in invasive disease-free survival. Extended adjuvant therapy with the irreversible pan-HER2 inhibit…