Optimal adjuvant cytotoxic therapy for breast cancer

The optimal adjuvant chemotherapy regimen for breast cancer may be changing in light of recent evidence. Classic cyclophosphamide. methotrexate, and 5-fluorouracil (CMF) chemotherapy has been in use for over 30 years, however the Oxford overviews suggest that CMF may be suboptimal compared with anthracycline regimens. particularly for tumours with adverse prognosis. Nevertheless, CMF remains a highly effective alternative to anthracyclines for women with low recurrence risk, or with high risk of cardiotoxicity. Although widely used as a standard regimen in North America, the cumulative dose and dose intensity of doxorubicin in 4AC (four cycles of doxorubicin and cyclophosphamide) may be suboptimal. Until there is confirmation of equivalence of 4AC with higher-dose anthracycline regimens in a randomized setting, the latter are preferable in women with high-risk early breast cancer. Early results of Cancer and Leukemia Group B (CALGB) 9344 reported significant improvements in disease-free and overall survival with the addition of paclitaxel to 4AC, however these results have not been duplicated thus far. Results from additional randomized adjuvant taxane trials involving 17 000 + women are needed to help define the adjuvant role of taxanes. Molecular markers may predict response to cytotoxic therapy, much like the presence of hormone receptors predicts response to hormonal therapies. It is hoped that our growing understanding of such markers will enable future matching of specific genetic aberrations of a tumour with the drugs most likely to work against or in spite of these deregulations. (C) 2001 Harcourt Publishers Ltd.