Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis

Hadar Goldvaser, Habeeb Majeed, Domen Ribnikar, Boštjan Šeruga, Alberto Ocaña, David W. Cescon, Eitan Amir*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Purpose: Results from clinical trials of adjuvant dose-dense chemotherapy in patients with breast cancer are inconsistent. Methods: A systematic search of MEDLINE identified studies comparing the efficacy of dose-dense adjuvant chemotherapy to a standard treatment. The primary analysis included studies that used identical regimens in the experimental and control groups, but varied only dose density. A secondary analysis included studies that used either different drugs or doses in the experimental and the control groups. Hazard ratios (HRs) and 95% confidence intervals were computed for disease-free survival (DFS) and overall survival (OS) and pooled in a meta-analysis. Subgroup analyses and meta-regression explored drug schedules utilized in control groups and the influence of clinicopathologic variables on benefit from dose-dense therapy. Results: The primary analysis included 5 studies comprising 9819 patients while the secondary analysis included 6 studies comprising 9679 patients. Dose-dense treatment significantly improved DFS (HR 0.85, p < 0.001) and OS (HR 0.86, p = 0.008) in the primary analysis. Similar results were observed in the secondary analysis. Dose-dense schedule was important primarily in studies utilizing paclitaxel every 3 weeks as the control group (interaction p = 0.04 for DFS interaction p = 0.001 for OS). A significantly greater relative magnitude of benefit was observed in pre-menopausal women and those with nodal involvement, but there was no influence of hormone receptor status on results. Conclusions: Adjuvant dose-dense regimens improve breast cancer outcomes. It remains uncertain whether the observed benefit reflects the impact of dose density or the inferiority of paclitaxel every 3 weeks as a control group.

Original languageEnglish
Pages (from-to)413-425
Number of pages13
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - 1 Jun 2018


  • Adjuvant
  • Breast cancer
  • Chemotherapy
  • Dose-dense
  • Neoadjuvant


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