High-Dose Chemotherapy in the Adjuvant Treatment of Breast Cancer: Benefit/Risk Analysis.

BACKGROUND: High-dose chemotherapy (HDRx) may improve the prognosis of patients with high-risk breast cancer but at the expense of increased toxicity. However, no randomized, controlled trials have been published that clearly demonstrate the superiority of HDRx over conventional adjuvant chemotherapy. METHODS: We developed a simple model to compare benefits and risks of HDRx with conventional adjuvant chemotherapy (SDRx). The model integrates data on efficacy and risks of two competing treatment strategies into a single decision rule. RESULTS AND CONCLUSIONS: Using data from phase II studies, we show that if a disease-free survival is considered to be the most important outcome, HDRx should be administered when the probability of breast cancer relapse at five years exceeds 54% to 71% for patients with 4 to 9 positive nodes and exceeds 29% to 40% for patients with >9 positive nodes. If the endpoint of interest is five-year overall survival, then the treatment should be administered when the probability of relapse exceeds 77% to 83% for patients with 4 to 9 nodes involved and 22% to 31% for those with >9 lymph nodes involved. While awaiting results of randomized, controlled trials to definitively establish the efficacy rate of HDRx, we also found that HDRx could be considered in the management of high-risk breast cancer if its efficacy rate is at least 54% to 60% superior to SDRx in reducing relapse risk in breast cancer patients with 4 to 9 nodes and at least 31% to 38% for >9 positive nodes. If survival data are used instead of disease-free survival outcomes, HDRx efficacy should be at least 47% to 48% superior to SDRx in reducing death risk in breast cancer patients with 4 to 9 nodes and at least 27% to 30% superior for >9 positive nodes to consider its use in the adjuvant setting.