| Background: Numerous randomized trials have demonstrated the survival benefits of adjuvant chemotherapy in operable breast cancer. However, the relationship between time to adjuvant chemotherapy and survival is unclear. We performed a systematic review and meta-analysis to declare the influence on survival of delaying initiation of adjuvant chemotherapy.Methods: Pub Med, EMBASE, Cochrane Database of Systematic Reviews, Web-ofScience and Google Scholar databases(between January-1 1978 and December-31, 2015) were searched for eligible studies that described the relationship between TTC and survival in breast cancer. 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 adjuvant chemotherapy. The adjusted β from individual studies were combined using a fixed-effects or random-effects model depending on heterogeneity. The summary measures of HR per 4-week of delay from each study was calculated by eβ*4.Results:11 eligible studies with 14 independent analytical groups were included in the analysis involving 77054 patients, 1 prospective observational study, 3 secondary analyses in randomized trials(5 analytical groups), and 7 hospital-/population-based retrospective study(8 analytical groups). The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS(HR=1.10;95% confidence interval [CI],1.06-1.15;random-effects model)and DFS(HR=1.09;95%CI,1.03-1.14; fixed-effects model).However, the heterogeneity for OS is significant(P = 0.003; I2 = 61.2%).After subgroup analysis on year, there was no heterogeneity(P = 0.604; I2 =0.0%),moreover, one study also caused a significant between-study heterogeneity for OS; after excluding that single study, that heterogeneity was significantly lower(P = 0.06; I2 =43.5%).Each single study did not fundamentally influence the positive outcome and no evidence of publication bias was observed in OS. The analyses were repeated for DFS. There was no evidence of heterogeneity(P = 0.623, I2 = 0.0%) or publication bias. Two studies categorized patients into hormone receptor–positive, ERBB2-positive and triple-negative breast cancer subgroups according to breast cancer subtype. HRs for OS between WT ≤30 days and 31-60 days in the three subgroups was extracted and analyzed. The subgroup analysis demonstrated that TTC 31-60 days was associated with worse OS among patients with TNBC(HR, 1.26; 95% CI, 1.08-1.48) but had no significant effect among those with hormone receptor–positive(HR, 1.02; 95% CI, 0.89-1.15) or ERBB2+(HR,0.95;95%CI, 0.79-1.14) tumors. There was no evidence of publication bias.Conclusions: a longer time to adjuvant chemotherapy may leads to worse survival in breast cancer patients, especially TNBC. |
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