Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

Abstract

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Keywords:

• breast cancer
• HER2-positive
• neratinib
• early-stage
• targeted therapy

Acknowledgments

Matteo Lambertini acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at Institut Jules Bordet. EdA and ML are co-last authors.

Disclosure

EdA received honoraria from Roche and travel grants from Roche and GlaxoSmithKline outside the submitted work. His institution has received research grants from Roche. The other authors report no conflicts of interest in this work.