HER2-positive breast cancer: update on Breast Cancer International Research Group trials

HER2 gene amplification occurs in approximately 20% of primary breast cancers and is associated with a poor prognosis. Recently, trastuzumab, a humanized murine monoclonal antibody directed against the extracellular domain of HER2, was introduced for the treatment of patients with HER2-overexpressing advanced breast cancer. Trastuzumab has activity as both a single agent and in combination with chemotherapy. However, trastuzumab in conjunction with anthracyclines produces an unacceptably high rate of cardiac toxicity, which has prompted the search for alternative regimens. Docetaxel and the platinum salts are logical candidates to be combined with trastuzumab since these agents exhibit potent synergy with the antibody in preclinical experiments. Furthermore, the available phase II clinical data using the TCH (docetaxel/platinum/trastuzumab) regimen suggest this combination has significant activity. The Breast Cancer International Research Group (BCIRG) 006 trial is a 3-arm adjuvant study comparing doxorubicin/cyclophosphamide followed by docetaxel, the same regimen with trastuzumab administered with docetaxel (TH), and TCH in 3150 women with node-positive or high-risk node-negative, HER2-positive breast cancer. BCIRG 007 compares TH and TCH as first-line therapy in patients with HER2-positive metastatic breast cancer. In both trials, entry is restricted to patients whose tumors are positive for HER2 gene amplification as determined by fluorescence in situ hybridization. The data from these trials, in addition to the results from other ongoing randomized studies, will help define the optimal way to utilize trastuzumab in the management of patients with HER2-positive breast cancer.