title: Association between delayed initiation of adjuvant CMF or anthracycline-based chemotherapy and survival in breast cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Adjuvant chemotherapy (AC) improves survival among patients with operable breast cancer. However, the effect of delay in AC initiation on survival is unclear. We performed a systematic review and meta-analysis to determine the relationship between time to AC and survival outcomes.
  
  
  METHODS
  PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Web-of-Science databases (between January-1 1978 and January-29, 2013) were searched for eligible studies. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) from each study were converted to a regression coefficient (β) corresponding to a continuous representation per 4-week delay of AC. Most used regimens of chemotherapy in included studies were CMF (cyclophosphamide, methotrexate, and fluorouracil) or anthracycline-based. Individual adjusted β were combined using a fixed-effects or random-effects model depending on heterogeneity.
  
  
  RESULTS
  We included 7 eligible studies with 9 independent analytical groups involving 34,097 patients, 1 prospective observational study, 2 secondary analyses in randomized trials (4 analytical groups), and 4 hospital-/population-based retrospective study. The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS (HR = 1.15; 95% confidence interval [CI], 1.03-1.28; random-effects model) and DFS (HR = 1.16; 95% CI, 1.01-1.33; fixed-effects model). One study caused a significant between-study heterogeneity for OS (P < 0.001; I² = 75.4%); after excluding that single study, there was no heterogeneity (P = 0.257; I² = 23.6%) and the HR was more significant (HR = 1.17; 95% CI, 1.12-1.22; fixed-effects model). Each single study did not fundamentally influence the positive outcome and no evidence of publication bias was observed in OS.
  
  
  CONCLUSIONS
  Longer time to AC is probably associated with worse survival in breast cancer patients.
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, 399 Ling-Ling Road, Shanghai 200032, People's Republic of China. yukd@shca.org.cn
authors.forename: Ke-Da
authors.initials: KD
authors.lastname: Yu
authors.forename: Sheng
authors.initials: S
authors.lastname: Huang
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Zhang
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Liu
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D061665:Time-to-Treatment