Dose-dense chemotherapy versus conventional chemotherapy for early breast cancer: A systematic review with meta-analysis

Background: Despite the widespread acceptance of dose-dense (DD) regimens as adjuvant chemotherapy for early breast cancer (EBC), studies of efficacy offer contradictory findings. This systematic review evaluates the real impact of DD chemotherapy. Methods: Randomized controlled trials comparing conventional adjuvant chemotherapy versus a DD regimen for EBC patients were searched in electronic databases. Dose-dense regimens included the same drugs and total amount as conventional chemotherapy, but applied in shorter intervals. Meta-analyses were performed using a fixed-effects model. Hazard ratios (HRs) or odds ratios (ORs) were expressed with 95% confidence intervals (95% CI). The outcomes were overall survival (OS), disease-free survival (DFS), and toxicities. Analyses were conducted according to tumor hormone receptor expression, plus tests for interaction. Results: Four studies (3418 patients) were included. The meta-analysis demonstrated that DD therapy can improve DFS (3356 patients; HR = 0.83; 95% CI 0.73-0.95; p = 0.005), independent of hormone receptor expression status. There was no OS benefit with DD therapy (3356 patients; HR = 0.86; 95% CI 0.73-1.01; p = 0.06) irrespective of tumor hormone receptor status (OS in hormone-positive stratum HR = 0.94; 95% CI 0.74-1.21; OS in hormone-negative stratum HR = 0.78; 95% CI 0.62-0.99; interaction test p = 0.28). DD regimens caused a small increase in anemia and mucositis, but had no impact on cardiac events, leukemia or myelodysplasia. Conclusions: DD adjuvant chemotherapy can improve DFS of EBC patients with little impact on safety. However there is no clear benefit in OS. Further research may indicate if there is any impact on OS not presently seen due to small sample size, and which patients may derive greater benefit. (C) 2012 Elsevier Ltd. All rights reserved.