Present status and potential role of high-dose adjuvant chemotherapy in breast cancer with poor prognosis

Abstract

Adjuvant systemic treatments have undoubtedly altered the natural course of resectable breast cancer in patients at high risk of relapse and death. Adjuvant chemotherapy has been demonstrated to produce moderate but consistent improvements in long-term disease-free and overall survival, mainly in premenopausal patients. These achievements have been obtained with regimens which are not curative in metastatic disease. The most extensively used regimens are based on cyclophosphamide, methotrexate and 5-fluorouracil (CMF). However, women with more than three histologically positive axillary lymph nodes still have a poor prognosis. In fact, after adjuvant standard CMF for 12 months more than half of these patients relapsed within 44 months and died within 82 months of surgery (in the Milan trial). Review of the data from International Breast Cancer Study Group adjuvant breast cancer trials shows that women with breast cancer four or more involving axillary lymph nodes have a 70% risk of relapse at 5 years and approximately 60% risk of death from their disease at 9 years after primary treatment with standard-dose adjuvant chemotherapy, regardless of menopausal and œstrogen status. The outcome of adjuvant systemic therapy might be dependent on the dose intensity of the regimens used. Dose reduction of chemotherapy, if given with curative intent, may lead to poor result. Dose escalation for CMF treatment proved not to be feasible because of subjective and objective toxicity.