Role of trastuzumab in the management of HER2-positive metastatic breast cancer

Andrea Milani^1,2, Filippo Montemurro¹, Luisa Gioeni¹, Massimo Aglietta^1,2, Giorgio Valabrega^1,2
1Oncological Department, Medical Oncology, Institute for Cancer Research and Treatment (IRCC), Candiolo, Torino, Italy; ²University of Turin Medical School, Department of Biomedical Sciences and Human Oncology, Turin, Italy

Abstract: Breast cancer is a major health issue in developed countries. Overexpression of HER2, a member of epidermal growth factor receptor family, occurs in 20%–30% of breast cancers. HER2 drives the cancer cells to develop a more aggressive phenotype, to metastasize to viscera and central nervous system, and to be less sensitive to chemotherapeutic agents. Trastuzumab (Herceptin^®) is a monoclonal antibody directed against the extracellular domain of HER2. As single agent or with chemotherapy, trastuzumab improves survival of HER2-positive breast cancers. In the past years, trastuzumab has completely revolutionized the scenario of the treatment of HER2-positive breast cancer, representing one of the most remarkable examples of targeted therapy in oncology. However, issues such as the best chemotherapeutic companion to associate with trastuzumab, cardiac toxicities, and clinical resistance still require tremendous efforts by researchers. Here, we review pharmacology, efficacy studies, and toxicities of trastuzumab in metastatic breast cancer. Moreover, we provide some insights on resistance to therapy. Finally, we briefly discuss trastuzumab’s place in the clinical setting.

Keywords: HER2, trastuzumab, breast cancer, cardiotoxicity, resistance