Assessment of the Prognostic Role of Ki-67 and Its Optimal Cutoff Value in Early Breast Cancer: A Retrospective Analysis

Abstract

Background: Breast cancer is a heterogenous group of diseases classified into the biological subtypes luminal A, luminal B, HER2-enriched and triple negative. These subtypes have different treatment response patterns and survival rates. Ki-67 is the most commonly used proliferative marker in breast cancer and is used for the distinction between luminal A and B subtypes. Methods: A retrospective study that included patients with early breast cancer diagnosed between 2010 and 2016 and treated in a single cancer center. Results: The medical records of 498 patients were retrospectively reviewed. The median age of patients was 51 years (range: 21 – 81) and the median value of Ki-67 level among them was 20% (interquartile range: 10-30%). Ki-67 was significantly higher in younger (<35 years) and premenopausal patients (p=0.0002 and 0.0055, respectively). Higher Ki-67 level associated significantly with higher T stage, estrogen and progesterone receptors-negativity, HER2-positivity and higher grade (p=0.0256, <0.0001, <0.0001, =0.0001 and =0.0031; respectively). Univariate Cox regression analysis showed that the ≥14% and ≥20% cutoff values of Ki-67 level are associated with poorer disease-free survival (DFS) (HR=1.989 [95%CI: 1.163-3.402, p=0.0121] and HR=1.616 [95%CI: 1.001-2.61, p=0.0496], respectively). On stratifying patients according to the Ki-67 proliferation index into three strata, <14%, ≥14%--<20% and ≥20%; DFS differed significantly between them (p=0.0394). The 5-year DFS rate for the three strata was 82.2%, 64.7% and 64.8%; respectively. Conclusion: Early breast cancer patients with lower Ki-67 levels have significantly better DFS. A Ki-67 cutoff value of ≥14% appears to correlate better with DFS than the newer cutoff value of ≥20%.