Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials

Dose-dense (DD) chemotherapy (CT) aimed at achieving a higher rate of cancer cell destruction has been adopted as an adjuvant therapy in high-risk breast cancer (BC), with the goal being to improve outcomes. We performed an updated systematic review and meta-analysis of the existing data from randomized phase III trials regarding the efficacy and toxicity of this adjuvant DD-CT strategy in early BC. Randomized-controlled trials that compared a DD with a standard adjuvant CT schedule in adult women with resected BC were identified by searching the databases of Pubmed, the Cochrane Cancer Register of Controlled Trials, SCOPUS, EMBASE, and the Web of Science up to March 2015. Hazard ratios (HRs) of death and recurrence, and the relative risks of adverse events, were estimated and pooled. A total of 8 phase III trials encompassing 17,188 randomized patients met the inclusion criteria. The patients who received DD-CT had better overall survival (OS: HR 0.86, 95 % confidence interval [CI] 0.79-0.93, P = 0.0001) and disease-free survival (DFS: HR 0.84, 95 % CI 0.77-0.91, P < 0.0001) than those on the conventional schedule. A statistically significant OS benefit was observed in patients with hormone receptor-negative (ER-) tumors (HR 0.8, P = 0.002), but not in those with ER-positive BC (HR 0.93, 95 % CI 0.82-1.05; P = 0.25). DD-CT leads to better OS and DFS, particularly in women with ER- early BC. These results suggest that the DD strategy should be the standard care offered to high-risk ER- BC patients.