The effect of delay in time to adjuvant chemotherapy (TTAC) on survival in breast cancer (BC): A systematic review and meta-analysis.

Abstract

1128 Background: The optimal timing from BC surgery to initiation of adjuvant chemotherapy (AC) is unknown. We report a systematic review and meta-analysis to determine the relationship between TTAC and survival. Methods: A systematic review of literature was completed to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. Publication bias was investigated using funnel plots and the trim-and-fill approach. Results: We identified 4 eligible studies for OS, and 5 for DFS, all fully published manuscripts. The OS studies involved 15,327 patients; two were randomized trials and 2 were cohort studies; one study reported TTAC as a binary variable and three had 4 TTAC categories. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with an OS HR of 1.06 (95% CI 1.02-1.10), and DFS HR of 1.08 (95% CI 1.03-1.14). The analyses for heterogeneity justified the use of a fixed-effect model. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the studies of largest weight. Conclusions: This study demonstrates a 6% increase in the risk of death for each 4 week delay to initiation of AC for BC. Our results were consistent for both OS and DFS, and remained significant after correction for publication bias. These findings indicate that clinicians and oncology health systems managers should monitor TTAC for quality assurance, and keep TTAC as short as reasonably achievable.