Advances in the management of HER2-positive early breast cancer

Abstract

While trastuzumab is firmly established as the cornerstone of therapy for both early and advanced breast cancer expressing human epidermal growth factor receptor 2 (HER2), many patients either do not respond to trastuzumab treatment or progress following therapy. Improved understanding of breast cancer biology, particularly the complex signaling interactions managed by the HER family of receptors, have resulted in development of several novel HER2-directed therapies and combinations. This article will review the novel approaches to HER2 targeting that have been developed in recent years, with particular focus on results from these approaches in early breast cancer, and will discuss strategies to improve the tolerability of HER2-directed therapies, including prevention of cardiac toxicity and diarrhea.

Target arm affinities determine preclinical efficacy and safety of anti-HER2/CD3 bispecific antibody

“…HER2 is a clinically validated target for multiple monoclonal antibodies, small molecule tyrosine kinase inhibitors, and the antibody-drug conjugate ado-trastuzumab emtansine (1). HER2 is a strong oncogenic driver of tumor cell growth due to overexpression or activating mutations.…”

GRB7 dependent proliferation of basal‐like, HER‐2 positive human breast cancer cell lines is mediated in part by HER‐1 signaling

“…This adverse prognosis however has improved significantly with the advent of effective HER‐2 targeted therapeutics. HER‐2 targeted therapeutics consist of humanized HER‐2 targeting monoclonal antibodies such as trastuzumab and pertuzumab, toxin antibody conjugate such as TDM1, and small molecule kinase inhibitors such as neratinib and lapatinib . Despite this success, there is still much room for improvement.…”

The evolving role of receptors as predictive biomarkers for metastatic breast cancer

“…Despite the improvement in prognosis of patients with HER2+ breast cancer since the introduction of anti-HER2 therapy (see sections 2.2. and 3.1), challenges remain in the management of these tumours, particularly in the advanced setting where overall response rates are often relatively limited and the high rates of de novo and acquired resistance frequently lead to tumour progression. While researchers continue to investigate alternative anti-HER2 and combination therapies for first and second line treatment [74,76,104,204], there is also a need to identify additional predictors to help improve treatment selection [205]. Most of the research to date has described alterations in associated pathways and downstream effectors of HER2 [206].…”