The Role of HER2-targeted Therapies in Women with HER2-Overexpressing Metastatic Breast Cancer

Abstract

The role of targeted therapies in the treatment of women with breast cancer has been rapidly evolving. Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), was the first HER2-targeted therapy that clearly demonstrated a significant clinical benefit for women with HER2-overexpressing metastatic breast cancer (MBC). Over the past few years however, it has become increasingly apparent that when trastuzumab is used in the ‘first–line’ setting in combination with chemotherapy, despite significant clinical benefit, the majority of women eventually develop progressive disease. The treatment options available to women who have progressed while on trastuzumab therapy have been hampered by a paucity of high quality published data. In addition, with the standard use of trastuzumab in the adjuvant setting (for eligible HER2-positive patients), the role of anti-HER2 agents for patients who relapse have become a clinically relevant question. This manuscript will review the current available data and outline suggestions from a panel of Canadian oncologists about the use of trastuzumab and other HER2-targeted agents in two key metastatic breast cancer (MBC) patient indications: • Treatment for women with HER2-positive MBC progressing on trastuzumab (i.e. treatment beyond progression) • Treatment for women with HER2-positive MBC recurring following adjuvant trastuzumab (i.e. re-treatment) The suggestions set out here will continue to evolve as data and future trials with trastuzumab and other HER2-targeted agents emerge.