Abstract
Amplification of the HER-2/neu gene resulting in overexpression of the p185HER-2 growth factor receptor occurs in approximately 25-30% of early stage breast cancers and is associated with a poor prognosis. HER-2/neu has also become a marker for predicting the response to anti-HER-2/neu monoclonal antibodies, which have been shown to improve the response rate, response duration, and overall survival in combination with chemotherapy in HER-2/neu amplified metastatic breast cancers. Recent data suggest an association between the degree of HER-2/neu overexpression and the response to anti-HER-2/neu monoclonal antibodies. HER-2/neu is also a potential predictive marker for response to chemotherapy or endocrine therapy. Controversies about the detection of HER-2/neu in archival breast tumor specimens and pitfalls of retrospective subgroup analysis complicate the interpretation of studies of the predictive value of HER-2/neu. As a result there is no conclusive evidence for resistence towards cyclophosphamide, methotrexate, and fluorouracil in HER-2/neu-positive breast cancers. Retrospective studies suggest an increased response to doxorubicin-containing chemotherapeutic regimens in HER-2/neu-positive breast cancers. Data on taxanes are inconclusive. HER-2/neu overexpression is also inversely associated with estrogen receptor (ER) positivity, but in cases where ER and HER-2/neu are coexpressed tamoxifen efficacy is in question. Large cooperative trials have not confirmed a deleterious effect of tamoxifen in such cases. In conclusion, HER-2/neu may be a useful marker for predicting the response to chemotherapy agents, antiestrogens, and therapeutic anti-HER-2/neu monoclonal antibodies.
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