Risk-Adapted Chemotherapy in the Adjuvant Setting of Breast Cancer

overall and disease-free survival in breast cancer patients. However, there are two major problems in the field of adjuvant chemotherapy: (1) The threshold of risk at which adjuvant cytotoxic chemotherapy is deemed necessary has become very low. The preliminary results of a large randomized US trial (NSABP B-20) showed that 5-year survival rates of women with good-prognosis early breast cancer (estrogen-receptor-positive/node-negative) was improved by 3% (from 94 to 97%) by the use of adjuvant cytotoxic chemotherapy in comparison to tamoxifen alone [1]. However, in contrast to node-positive patients, 60–70% of node-negative patients are cured by locoregional surgery and radiotherapy alone. Until now the recommendations for adjuvant chemotherapy in node-negative cancer depend on age, tumor size, grading and hormone receptor expression. It would be of advantage if high-risk, node-negative patients could be selected for adjuvant chemotherapy by different prognostic factors. Factors capable of quantifying the invasive and metastatic capacity of malignant cells should be suitable for estimation of prognosis. Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the tumor matrix and the basement membranes. The urokinase-type plasminogen activator uPA and its inhibitor PAI-1 are strong and independent prognostic markers in breast cancer [2]. Since uPA and PAI-1 are independent prognostic factors, highor low-risk patients can be identified even within the classical risk groups defined by lymph node status, hormone receptor status or menopausal status. This might be of importance for clinical decision-making in node-negative breast cancer in the future. (2) According to the 1998 St. Gallen Consensus Conference, CMF (cyclophosphamide, methotrexate, fluorouracil) or AC (doxorubicin, cyclophosphamide) is still the standard of care for node-negative and all node-positive breast cancer patients. However, we have accumulating data that at least CMF is no longer the gold standard in the adjuvant treatment of high-risk breast cancer patients with ≥ 4 positive nodes, and these patients will receive inadequate treatment. Editorial