Treatment of metastatic ErbB2-positive breast cancer: options after progression on trastuzumab.

Although trastuzumab-based therapy has changed the treatment paradigm for ErbB2-positive breast cancers, most patients eventually develop progressive disease. Of particular interest is the issue of disease progression in the central nervous system, a safe haven from high molecular weight antibodies like trastuzumab, which have limited ability to cross the blood-brain barrier. This review will discuss therapeutic options for when disease progression has occurred on trastuzumab-based therapies, including central nervous system progression, continuation of trastuzumab-based therapy, addition of novel targeted therapies, and the use of small-molecule tyrosine kinase inhibitors targeting ErbB receptors.