Accuracy of Ki-67 with Recurrence Score and Recurrence Score -Pathology - Clinical Assessment in Early Stage Breast Cancer

Background: Ki-67 is a cellular marker of proliferation in breast cancer but varied scoring methods and standardization of the assays have limited its clinical utility. The Recurrence Score Pathology - Clinical (RSPC) value integrates the Recurrence Score (RS) with tumor grade, tumor size, and patient age and has been suggested to provide additional prognostic value and greater accuracy in the assessment of distant recurrence risk than RS. Many patients in El Paso, TX, with breast cancer have limited resources and are unable to receive relatively expensive diagnostic assays. We sought to compare the diagnostic performance of Ki-67 with RS and RSPC to determine the clinical validity of using Ki-67 as a prognostic tool. Methods: Patients with early stage estrogen receptor or progesterone receptor positive breast cancer were assessed for Ki-67 indices using an immunohistochemical method. Ki-67 was considered as low < 20%, intermediate 20-50%, and high > 50%. RSPC was calculated using a risk assessment tool, with low < 12%, intermediate 18-20%, and high > 20% cutoffs. Raw agreement and weighted Kappa agreement were obtained between Ki-67, RS, and RSPC. McNemar's test was used to compare the proportion of discordant pairs between Ki-67, RS, and RSPC. In addition, sensitivity, specificity, and predictive values of Ki-67 in relation with RSPC and RS were calculated after dichotomizing these measures. Results: The accuracy of Ki-67 with RS was observed as 51% while with RSPC as 55%. A very good concordance was found between low Ki-67 and low RSPC (80.9%) while a moderate concordance was observed between low Ki-67 and low RS (55%). We also observed a moderate concordance between high Ki-67 and high RS (50%). The concordance between intermediate Ki-67 and RS was found to be moderate (46%) and with intermediate RSPC was observed to be 30%. Specificities of Ki-67 with RS and RSPC (for classifying high or intermediate) were found as 68.3% and 80.5% respectively. The positive predictive values of Ki-67 with RS and RSPC (for classifying high or intermediate) were observed as 63.9% and 72.4% respectively. Conclusion: Ki-67 provides a very good concordance with RSPC. Ki-67 provides a moderate concordance with RS for low risk (Ki-67 < 20% as cut off) as well as for RSPC and RS for high risk group (Ki-67 > 50%). High specificity of Ki-67 shows that Ki-67 can be used for clinical decision making. Ki-67 can be used reliably for clinical decision making, particularly in low and high risk groups in the absence of RS or RSPC. This has significant clinical and cost implications for many early stage breast cancer patients with limited resources.