Trastuzumab and lapatinib beyond trastuzumab progression for metastatic breast cancer: strategies and pitfalls

The discovery of HER2 gene amplification and protein overexpression in approximately 15-20% of breast cancers and access to the tailored humanized antibody, trastuzumab (Herceptin(R)), have heralded a new era in breast cancer therapy. Trastuzumab combined with chemotherapy has caused marked tumor responses and increased overall survival in patients with metastatic breast cancer, and has also increased survival in the adjuvant setting after radical surgery. However, due to many causes, trastuzumab resistance usually occurs during treatment. In this event, possible options include the replacement of trastuzumab with lapatinib, the continuation of trastuzumab after disease progression with changed chemotherapy and the suspension of the use of targeted agents. New-generation tyrosine kinase inhibitors, which have a broader target, are now considered the key to treatment for breast cancer.