Trastuzumab Resistance: What Are We Offering to Breast Cancer Patients?

Human epidermal growth factor receptor-2 (HER2/ErbB-2) is a receptor tyrosine kinase involved in cell growth and differentiation and over-expressed in about 15-30% of breast cancers. Trastuzumab is an anti-HER2 monoclonal antibody that has significantly improved survival of patients with early and metastatic breast cancer (BC). However, 65% patients experience primary and secondary resistance. This article explores existing and emerging combination therapy for HER2 positive breast cancer, highlighting the success of trastuzumab in combination with another monoclonal antibody, pertuzumab and small molecule tyrosine kinase inhibitors lapatinib and neratinib. Recent studies have indicated that combination of trastuzumab, pertuzumab and lapatinib increases the 3-year overall survival from 90% to 95% in metastatic BC patients. The EPHOS-B trial has shown a remarkable shrinkage of the tumour when lapatinib is used before surgery and chemotherapy. Despite this success, pertuzumab has just been approved for use in the British National Health Service (NHS) while pertuzuamb, lapatinib and neratinib have been approved for European and American markets for a number of years. Lapatinib and neratinib are not available yet in UK. Strict assessment criteria on cost-benefits might limit the access to these drugs to British cancer patients.