Treatment of HER2 positive breast cancer patients

Abstract

Breast cancer (BC) is the most common cancer in women. It is known already for years that BC is a heterogeneous disease. This has now been confirmed by BC gene signature by which at least four types of BC subtypes can be distinguished. Approximately 15 % of patients with BC have a »HER2 like« tumor. A distinctive feature of this subtype is an overexpression of HER2 protein and/or amplification of the HER2 gene. HER2 protein is a transmembrane receptor protein, which promotes tumor growth, replication, invasion and dissemination. Consequently, when diagnosed, HER2 positive tumors are usually larger, less-differentiated, and are more often accompanied by metastatic involvement of the axillary lymph nodes, as compared to HER2 negative tumors. Women with HER2 positive tumors are therefore at higher risk of cancer recurrence and death. With the introduction of targeted anti- HER2 therapy, the prognosis of HER2 disease has significantly improved. There are currently two antiHER2 drugs registered for use in general oncology practice. Trastuzumab is a monoclonal antibody directed toward the extracellular domain of HER2 protein. It is used for the treatment of metastatic BC and in adjuvant setting. It is more effective when combined with chemotherapy compared to monotherapy. Combined with chemotherapy, it prolongs time to progression and overall survival of patients with metastatic BC. A year of adjuvant treatment with trastuzumab reduces the risk of recurrence and death from BC by 50 % and 30 %, respectively. Lapatinib is a small molecule that binds to the intracellular domain of HER2 receptor. The drug is registered for the treatment of metastatic HER2 positive BC after failure to trastuzuamb therapy. Combined with chemotherapy or hormonal therapy, lapatinib prolongs time to progression in patients with metastatic BC. Several other antiHER2 drugs are currently under evaluation in clinical trials.