HER-2-targeted therapy: lessons learned and future directions.

HER-2 is overexpressed in 20-25% of invasive breast cancers and is associated with an aggressive tumor phenotype and reduced survival rates. The HER-2 status of a tumor is the critical determinant of response to the HER-2-targeted antibody trastuzumab. Thus, accurate assessment of HER-2 expression levels is essential for identifying breast cancer patients who will benefit from HER-2-targeted therapy. Trastuzumab combined with chemotherapy increases response rates, time to progression, and survival. However, the majority of cancers that initially respond to trastuzumab begin to progress again within 1 year. This minireview describes HER-2 targeting strategies currently in use or in stages of development for the treatment of breast cancer.