Targeted therapy of breast cancer

Breast cancer is the most frequent tumor of women. The development of effective adjuvant therapy based on postoperative administration of short-term chemotherapy (4-6 months) or long-term hormone therapy (5 years) or both, significantly improved survival of patients. However, therapy of adjuvant/metastatic disease is still palliative with a very low probability to induce complete remission and definitive cure of disease. The relevant efforts of basic research to identify the key and selective molecular alterations, which sustain breast cancer growth and progression allowed the possibility to develop specific molecular target treatments. Trastuzumab, a humanized monoclonal antibody to HER-2, is the first molecular targeting agent approved for therapy of metastatic breast cancer, capable to significantly improve clinical outcome in combination with cytotoxic therapy. Recent preliminary data from randomized, prospective, clinical trials suggest that trastuzumab decreases the risk of early recurrence by 50% in patients with HER-2-positive disease. Other novel targeted treatments are in clinical evaluation, including antiangiogenic compounds (Bevacizumab, sunitinib, vatalanib, and others) and bi-functional drugs such as lapatinib (anti Her-2 and EGFR agent) showing promising activity. This review provides an updated overview of the status of development of targeted therapy in breast cancer, as well as the challenges related to the rational use of molecular targeting agents.