Innovative Therapeutic Approaches for Patients with HER2-Positive Breast Cancer.

Abstract

Overexpression of human epidermal growth factor receptor 2 (HER2), a transmembrane tyrosine kinase receptor, has been described in about 15-20% of breast cancer (BC) and is associated with poor outcomes. Trastuzumab is the first anti-HER2 monoclonal antibody (mAB) that blocks receptor activity but it also activates immune response against cancer cells, thus, revolutionizing the prognosis of patients with HER2-positive BC. Over the years, new therapies have been developed, including other mAbs and tyrosine kinase inhibitors (TKIs) that required multimodal approaches with chemotherapy to optimize their anticancer activity. This chapter gives a comprehensive overview of the last advancements including new approaches and future combinations, which seem to be very promising in overcoming resistance to the traditional anti-HER2 treatments. A modern therapeutic algorithm should include treatment options based on tumour patterns and a patient-centred approach. A proper patient's selection is crucial to derive maximal benefits from a treatment strategy and emerging biomarkers should be integrated along with the HER2 status, which is currently the only validated biomarker in the context of HER2-positive disease. These biomarkers might include molecular features with reported prognostic/predictive significance, such as phosphatidylinositol 3' -kinase (PI3K) or mitogen-activated protein kinase (MAPK) pathways, programmed cell death protein ligand 1 (PD-L1), and tumour-infiltrating lymphocytes (TILs), which all affect prognosis and response to treatments.