Optimal treatment of early stage HER2-positive breast cancer

Significant advances have occurred in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer that have changed its natural history. The addition of trastuzumab to standard therapy has dramatically improved the prognosis for patients with early stage, HER2-positive breast cancer to unprecedented survival outcomes. Yet, long-term follow-up data from adjuvant pivotal trials indicate that 15-24% of patients still develop recurrent disease. Most of the research has focused on the addition of novel anti-HER2 drugs to standard therapy, including studies evaluating the monoclonal antibody pertuzumab; the antibody-drug conjugate trastuzumab-emtansine (T-DM1); the selective, reversible HER2/epidermal growth factor receptor kinase inhibitor lapatinib; or the irreversible pan-HER2 inhibitor neratinib. Dual HER2 blockade has improved overall survival remarkably in metastatic breast cancer; however, in patients with early stage disease, it has led to small benefits in progression-free survival. Moreover, biologic heterogeneity within HER2-positive disease may determine response to treatment and prognosis. Different subgroups of patients with HER2-positive breast cancer may benefit from different therapeutic approaches. Thus, there is ongoing work to optimize and de-escalate treatment in patients who may do just as well with less therapy and can avoid unnecessary treatments and their related toxicities. The objective of this review is to summarize the background and latest evidence on the current management of early stage, HER2-positive breast cancer and to present novel perspectives on its management.