Anti-HER2 neoadjuvant and adjuvant therapies in HER2 positive breast cancer

Since the introduction of anti-Her2 agents, the prognosis of HER2 positive breast cancer patients significantly improved. In the adjuvant setting, the monoclonal antibody trastuzumab has been evaluated in six randomized trials including more than 10,000 patients. Different modes of administration (concurrent versus sequential), durations (one year, two years or 9 weeks) and different chemotherapy regimens have been evaluated. To date, one year of trastuzumab in combination or after chemotherapy is the standard adjuvant therapy for patients with HER2 overexpressing tumors. Cardiac safety is still a major clinical issue, in particular in the treatment of early breast cancer. Several large randomized trials exploring shorter, and potentially less toxic, regimens are ongoing across several European countries. In the neoadjuvant setting, the addition of trastuzumab to chemotherapy resulted in a significantly higher activity as compared to chemotherapy alone. Unfortunately, primary and secondary resistance to trastuzumab is observed both in early and advanced disease. Several mechanisms are described as possible determinants of trastuzumab failure, and several new antiHER2 strategies are in development. Lapatinib, the HER1-2 TK inhibitor is currently approved in advanced disease after trastuzumab failure. Lapatinib is under evaluation in a large adjuvant trial, and in several neoadjuvant studies. Other molecules such pertuzumab, which binds the HER2 dimerization domain, or the pan-erbB TK inhibitor neratinib are under evaluation in the (neo)-adjuvant setting.