HER2/neu as a predictive factor in breast cancer.

One of the current trends in breast cancer research is to identify markers that can predict response to specific anticancer therapies; intense laboratory research and therapeutic trials are exploiting this strategy. The combination of cytotoxic drugs directed at the tumor population with the highest probability of being sensitive to them with molecules targeted at intracellular signaling and cell cycle control pathways, which may be deregulated as part of the malignant process, represents our best hope for improved survival in both early and advanced disease. The transmembrane tyrosine kinase receptor, HER2/neu, has been the subject of much investigation with respect to its prognostic value, predictive value, and as a target of antibody-mediated therapy. Retrospective evidence strongly suggests that HER2 overexpression is associated with decreased disease-free and overall survival in node-positive, and possibly also node-negative, breast cancer. Prospective trials have demonstrated that antibodies to HER2 can produce tumor responses in women with advanced disease that overexpresses this molecule. Moreover, the combination of such antibodies with cytotoxic drugs has been one of the few recent strategies to improve survival duration in metastatic breast cancer. The evidence supporting the role of HER2 as a factor predictive of response to hormone therapy and cytotoxic drugs is more ambiguous and requires prospective assessment. The available literature is reviewed herein, with a focus on the predictive value of HER2, potential mechanisms of resistance and sensitivity to various drugs, and future research directions involving this important molecule.