Abstract P1-13-07: Association Between Delayed Initiation of Adjuvant Chemotherapy and Survival in Breast Cancer: A Single-institution Study and A Systematic Review and Meta-analysis

Abstract

Abstract Objective: 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 single-institution data analysis and 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 (before March-20, 2012) were searched to identify relevant eligible studies. An additional retrospective analysis including 1,408 patients from the prospectively maintained database of Shanghai Cancer Center was performed and results were also included. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) from each study were converted to a regression coefficient (β) and its standard error corresponding to a continuous representation per 4-week delay of AC. Individual adjusted β were combined using a fixed-effects or random-effects model depending on heterogeneity. Results: We included 8 eligible studies with 10 independent analytical groups involving 21,221 patients, 1 prospective observational study, 2 secondary analyses in randomized trials (4 analytical groups), and 5 hospital-/population-based retrospective studies. In our single-institution study, every 4-week delay in initiation of AC significantly decreased OS (HR = 1.38; 95% confidence interval [CI], 1.03–1.87) and DFS (HR = 1.35; 95% CI, 1.08–1.69) after adjustment for other prognostic variables. The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS (HR = 1.20; 95% CI, 1.03–1.39; random-effects model) and DFS (HR = 1.21; 95% CI, 1.08–1.36; fixed-effects model). One study caused a significant between-study heterogeneity for OS (p = 0.001; I2=74.1%); after excluding that single study, there was no heterogeneity (p = 0.345; I2=11.1%) and the HR was more significant (HR = 1.24; 95% CI, 1.14–1.35; P < 0.001; fixed-effects model). Our single-institution data did not fundamentally influence the positive outcomes, since the HR of OS was 1.17 (95% CI, 1.00–1.37; random-effects model) after removing our study. No evidence of publication bias was observed either in OS or in DFS. Conclusion: The present meta-analysis suggests that longer time to AC was associated with worse survival in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-07.