Biomarkers for predicting response to anti-HER2 agents

Abstract

The HER2 receptor is amplified or overexpressed in approximately 20% of all breast cancers, but despite significant efforts of the clinical research community and a growing number of anti-HER2 agents, a significant number of patients with HER2-positive breast cancer either progress or suffer disease relapse within 5–10 years. The development of robust biomarkers that predict response to anti-HER2 agents is therefore an important clinical need to prevent overtreatment and to enable earlier assignment of patients to more optimal therapies. Here we review some of the recent advances in the field by focusing on pathways mediating resistance to anti-HER2 therapies, and the role of the immune system and cancer stem cells in therapy response. We also review preoperative treatment strategies and research paradigms that show promise in identifying novel biomarkers of response while also enabling the delineation of the mechanisms underlying clinical benefit from anti-HER2 therapies.