What can we learn from Herceptin trials in metastatic breast cancer?

Herceptin (trastuzumab), an anti-HER2 monoclonal antibody, is the first oncogene-targeted therapy to be developed for the treatment of metastatic breast cancer. The Herceptin clinical trial program has demonstrated that treatment with Herceptin provides substantial clinical benefits when used either as monotherapy or in combination with a number of chemotherapeutic agents. Of note, accurate assessment of HER2 status is essential to ensure that the patients most likely to benefit from Herceptin are identified: patients with immunohistochemistry (IHC) 3+ or fluorescence in-situ hybridization (FISH)-positive disease gain the greatest clinical benefits. In addition, clinical benefits appear to be greater the earlier Herceptin is used, although there is currently no direct clinical evidence to indicate whether an initial strategy of combination therapy is better than monotherapy or vice versa. Herceptin has been shown to be generally well tolerated. The most severe adverse events are rare serious infusion-related reactions and cardiotoxicity. These adverse events can be managed by standard care and patients at risk can often be identified prior to the initiation of Herceptin treatment. Currently, Herceptin should be given until disease progression, but there could be benefit in continuing treatment beyond disease progression.