[Breast cancer: HER2 changes one's cards on the table]

Recently, preliminary results of several randomized studies using trastuzumab in the adjuvant or neoadjuvant treatment of HER2-positive breast cancer have been reported. In the neoadjuvant setting, patients have been randomized to receive either chemotherapy alone (Group I), 4 cycles of paclitaxel followed by FEC (fluorouracil, epirubicin, cyclophosphamide) fo 4 cycles, or the same chemotherapy with concomitant weekly trastuzumab for 24 weeks (Group II). Pathologic complete responses were 25% in Group I and 66.7% in Group II, showing a significant superiority of treatment including trastuzumab. Among several ongoing studies of adjuvant therapy with trastuzumab, NSABP B-31 trial and NCCTG N9831 trial compared a standard treatment of sequential AC (doxorubicin, cyclophosphamide) followed by paclitaxel to the same chemotherapy regimen in combination with weekly trastuzumab for 1 year. In a third study (HERA trial), patients were randomized to 3 arms following adjuvant chemotherapy: observation, triweekly trastuzumab for 1 year or for 2 years. Joint analysis of B-31 and N9831 trials and interim analysis of patients randomized to receive 1 year trastuzumab in the HERA trial, show a significant improvement in disease-free survival with chemotherapy combined with trastuzumab. Treatment has been generally well tolerated with acceptable cardiotoxic effects (< 4%). However, the short follow-up precludes any information about long-term side-effects. Overall, although the risk/benefit ratio is in favor of trastuzumab including regimens, the use of this monoclonal antibody in the neoadjuvant or adjuvant treatment of HER2-positive breast cancer, should be carefully discussed with the patient.