The relationship between time to initiation of adjuvant chemotherapy and survival in breast cancer: a systematic review and meta-analysis

Breast Cancer Res Treat. 2016 Nov;160(1):17-28. doi: 10.1007/s10549-016-3960-3. Epub 2016 Sep 8.


Background: It is known that adjuvant chemotherapy improves survival in women with breast cancer. It is not known whether the interval between surgery and the initiation of chemotherapy influences its effectiveness.

Purpose: To determine the relationship between time to initiation of adjuvant chemotherapy and survival in women with breast cancer, through a systematic review of the literature and meta-analysis.

Methods: Systematic review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Controlled Trials, Google Scholar, and abstracts presented at major international oncology conferences. The primary meta-analysis included only high-validity studies which directly measured the time from surgery to initiation of adjuvant chemotherapy and which controlled for major prognostic factors. Outcomes reported in the original studies were converted to a regression coefficient (β) and standard error corresponding to a 4-week delay in the initiation of chemotherapy. These relative risks were combined in both fixed- and random-effects models. Homogeneity was assessed by the Cochran χ 2 statistic and the I 2 statistic. Potential publication bias was investigated using standard error-based funnel plots.

Results: Meta-analysis of 8 high-validity studies demonstrated that a 4-week increase in TTAC was associated with a significant increase in the risk of death in both the fixed-effects model (RR 1.04; 95 % CI, 1.01-1.08) and random-effects model (RR 1.08; 95 % CI, 1.01-1.15). The association remained significant when the most highly weighted studies were sequentially removed from this analysis, and also when additional, lower validity studies were included in this analysis. Funnel plots showed no significant asymmetry to suggest publication bias.

Conclusions: Increased waiting time from surgery to initiation of adjuvant chemotherapy is associated with a significant decrease in survival. Avoidance of unnecessary delays in the initiation of adjuvant chemotherapy has the potential to save the lives of many women with breast cancer.

Keywords: Adjuvant chemotherapy; Breast neoplasms; Meta-analysis; Survival rate; Time to treatment; Treatment outcomes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / mortality*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Mortality
  • Population Surveillance
  • Proportional Hazards Models
  • Reproducibility of Results
  • Risk
  • Time-to-Treatment
  • Treatment Outcome