Ki-67 as a prognostic molecular marker in routine clinical use in breast cancer patients.

Introduction: The proliferation biomarker Ki-67 is a prognostic factor for breast cancer that has been investigated in several retrospective studies and a few prospective ones. The aims of the present study were to examine interactions between Ki-67 and other biomarkers in breast cancer patients and to assess the relationship of Ki-67 to histological grading.
Patients and Methods: Patients with uniform immunohistochemical staining of Ki-67 by MIB-1 were identified from the database of the University Breast Center for Franconia. Data were available for 1232 of 2523 patients with invasive breast cancer who had been treated between 1998 and 2005. Ki-67 index was determined during routine work-up of the breast cancers by several surgical pathologists according to a standardized procedure. The Ki-67 proliferation index was correlated with hormone receptor status, HER2/neu status, age, tumor staging, and prognosis. In routine clinical practice, the grading was assessed according to Elston and Ellis, along with all other parameters.
Results: Ki-67 proliferation index>or=20% was found to be associated with all of the prognostic factors that were tested. However, it also maintained statistical significance relative to poor overall survival in a multivariate Cox proportional hazards model (hazards ratio 1.81; 95% CI, 1.17-2.78). The hazards ratio for disease-free survival did not reach statistical significance (HR 1.41; 95% CI, 0.95-2.09; P=0.086). However, in both models the grade was not an independent prognostic factor.
Conclusions: For routine clinical purposes, grading appears to add only limited information about the prognosis in comparison with Ki-67 expression. Further investigation of quality assurance for grading and of Ki-67 as a prognostic and predictive factor is warranted.