Evidence for the use of chemotherapy in breast cancer

Several distinct historical phases mark the evolution of chemotherapy for breast cancer, including the introduction of single agents in the 1960s, the development of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based regimens in the 1970s, the evaluation of the anthracyclines in the 1980s, and the incorporation of the taxanes in the 1990s. The greatest benefit from the use of standard combination chemotherapy occurs in the adjuvant setting, where absolute improvements in overall survival on the order of 10% have been achieved. In contrast, advances have been more modest in the treatment of metastatic disease, and novel agents and regimens are required for further progress. Of the new cytotoxic drugs introduced in the past decade, the taxanes and capecitabine appear to be the most promising, and have demonstrated activity alone and in combination for the treatment of metastatic disease. The introduction of trastuzumab, an antibody directed against the HER2 receptor protein, heralded the birth of targeted molecular therapy against breast cancer. It is clear that in the near future the further evaluation of trastuzumab combinations and the development of additional molecular agents will propel clinical breast cancer research. One of the main challenges of the new era will be identifying and validating predictive factors so that therapy may be individualized based on tumor biology, rather than empirically selected.