Tailoring the Treatment of Early-stage HER2-positive Breast Cancer: One Size Does Not Fit All

Abstract

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer accounts for 15% of all breast cancers and this cancer subtype was historically associated with poor outcomes. The development of HER2-directed therapies has dramatically improved outcomes for patients with early and advanced HER2+ disease. Trastuzumab is a HER2-targeted monoclonal antibody first approved for the treatment of advanced breast cancer in the late 1990s. Since then, it has been shown to improve long-term outcomes for patients with early-stage disease, particularly when given in combination with chemotherapy in the (neo)adjuvant setting. Pertuzumab is another monoclonal antibody that targets a different domain of the HER2 receptor from trastuzumab and prevents HER2–HER3 dimerization. The addition of pertuzumab to trastuzumab and chemotherapy improved long-term outcomes for patients with advanced disease; this drug has also been studied in the (neo)adjuvant setting and proved to improve long-term outcomes for patients with lymph node involvement. Neratinib and trastuzumab emtansine in the adjuvant setting have been shown to improve outcomes for selected high-risk patients. As more effective treatment options have been developed for the treatment of HER2+ breast cancer, we have progressively moved from a one-size-fits-all approach towards a tailored paradigm. In this narrative review, we summarize the diagnosis and prognosis of early-stage HER2+ breast cancer, as well as current treatment approaches.