Ki-67 Expression as a Factor Predicting Recurrence of Ductal Carcinoma In Situ of the Breast: A Systematic Review and Meta-Analysis

Ki-67 is a marker of proliferating cells; this meta-analysis of cohort studies highlights that higher Ki-67 expression predicts recurrence rates in breast ductal carcinoma in situ. The predictive role of Ki-67 expression seems independent of cut-off level and is evident in adjusted as well as unadjusted studies, regarding non-invasive as well as invasive recurrence. Background: Ki-67 is a marker of proliferating cells; in this meta-analysis we aimed to examine whether Ki-67 expression can predict recurrence rates of breast ductal carcinoma in situ (DCIS). Materials and Methods: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to April 30, 2017. Random effects (DerSimonian–Laird) models were used for the calculation of pooled relative risk (RR) estimates; meta-regression analysis was also performed. Separate analyses were performed according to Ki-67 expression cutoff levels, invasiveness of recurrence, and adjustment of studies. Results: Ten eligible cohort studies were synthesized; a significant association between Ki-67 expression and DCIS recurrence was noted for the Ki-67 cutoff at 10% (RR = 1.66; 95% confidence interval [CI], 1.14-2.42) as well as the Ki-67 cutoff at 14% (RR = 1.67; 95% CI, 1.01-2.77). Subanalysis on unadjusted (RR = 1.48; 95% CI, 1.06-2.07) and adjusted studies (RR = 2.19; 95% CI, 1.42-3.38) replicated the statistically significant findings. Ki-67 expression predicted the risk of invasive (RR = 1.53; 95% CI, 1.14-2.06) and noninvasive (RR = 1.59; 95% CI, 1.19-2.13) recurrence. Conclusion: This meta-analysis highlights Ki-67 expression as a predictor of DCIS recurrence; nevertheless, additional adjusted studies, with adequate follow-up periods, stemming from various world regions seem to be needed on this topic. © 2017 Elsevier Inc.