Subspecialized breast pathologists have suboptimal interobserver agreement in Ki-67 evaluation using 20% as the cutoff.

PURPOSE: Ki-67 expression levels in breast cancer have prognostic and predictive significance. Therefore, accurate Ki-67 evaluation is important for optimal patient care. Although an algorithm developed by the International Ki-67 in Breast Cancer Working Group (IKWG) improves interobserver variability, it is tedious and time-consuming. In this study, we simplify IKWG algorithm and evaluate its interobserver agreement among breast pathologists in Ki-67 evaluation. METHODS: Six subspecialized breast pathologists (4 juniors, 2 seniors) assessed the percentage of positive cells in 5% increments in 57 immunostained Ki-67 slides. The time spent on each slide was recorded. Two rounds of ring study (R1, R2) were performed before and after training with the modified IKWG algorithm (eyeballing method at 400× instead of counting 100 tumor nuclei per area). Concordance was assessed using Kendall's and Kappa coefficients. RESULTS: Analysis of ordinal scale ratings for all categories with 5% increments showed almost perfect agreement in R1 (0.821) and substantial in R2 (0.793); Seniors and juniors had substantial agreement in R1 (0.718 vs. 0.649) and R2 (0.756 vs. 0.658). In dichotomous scale analysis using 20% as the cutoff, the overall agreement was moderate in R1 (0.437) and R2 (0.479), among seniors (R1: 0.436; R2: 0.437) and juniors (R1: 0.445; R2: 0.505). Average scoring time per case was higher in R2 (71 vs. 37 s). CONCLUSION: The modified IKWG algorithm does not significantly improve interobserver agreement. A better algorithm or assistance from digital image analysis is needed to improve interobserver variability in Ki-67 evaluation.

Low interobserver agreement among subspecialised breast pathologists in evaluating HER2-low breast cancer.

AIMS: Metastatic HER2-low breast cancer (HLBC) can be treated by trastuzumab deruxtecan. Assessment of low levels of HER2 protein expression suffers from poor interobserver reproducibility. The aim of the study was to evaluate the interobserver agreement among subspecialised breast pathologists and develop a practical algorithm for assessing HLBC. METHODS: Six breast pathologists (4 juniors, 2 seniors) evaluated 106 HER2 immunostained slides with 0/1+expression. Two rounds (R1, R2) of ring study were performed before and after training with a modified Ki-67 algorithm, and concordance was assessed. RESULTS: Agreement with 5% increments increased from substantial to almost perfect (R1: 0.796, R2: 0.804), and remained substantial for three categories (<1% vs 1%-10% vs >10%) (R1: 0.768, R2: 0.764). Seniors and juniors had almost perfect agreement with 5% increments (R1: 0.859 and 0.821, R2: 0.872 and 0.813). For the three categories, agreement remained almost perfect among seniors (R1: 0.837, R2: 0.860) and substantial among juniors (R1: 0.792, R2: 0.768). Binary analysis showed suboptimal agreement, decreasing for both juniors and seniors from substantial (R1: 0.650 and 0.620) to moderate (R2: 0.560 and 0.554) using the 1% cut-off, and increasing from moderate to substantial (R1: 0.478, R2: 0.712) among seniors but remaining moderate (R1: 0.576, R2: 0.465) among juniors using the 10% cut-off. The average scoring time per case was higher (72 vs 92 s). CONCLUSIONS: Subspecialised breast pathologists have suboptimal agreement for immunohistochemical evaluation of HLBC using the modified Ki-67 methodology. An urgent need remains for a new assay/algorithm to reliably evaluate HLBC.