Abstract P1-03-02: Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours

Abstract

Abstract Background Regional differences in proliferative activity are commonly seen within breast cancers, but little is known on the degree of intratumoral heterogeneity of Ki67 expression. Our aim was to study intratumoral heterogeneity of Ki67 expression in early breast cancers and its association with clinicopathological features like estrogen receptor (ER) status, grade and histological type. Methods The Ki67-labelling index (Ki67-LI) was assessed in hot, cold and intermediate spots of 233 invasive breast cancers by counting a total of 1020 cells, according to a protocol of the International Ki67 in Breast Cancer Working Group. Differences between the spots per tumor were further analyzed for clinicopathological subgroups defined by ER status, grade and histological type. Results All clinicopathological subgroups showed significant differences in Ki67-LI between hot, intermediate and cold spots (p <0.001). The coefficient of variance (CV) between the spots was higher in ER positive than in ER negative cancers (72.6% vs 49.2%, p <0.001), and was highest in grade 3 (96.12%), grade 1 (87.27%) and invasive lobular tumors (83.59%), and lowest in medullary (26.48%) cancers. Nested analysis of variance indicated that in both ER positive and ER negative cancers, variance in Ki67-LI within tumours contributed more to the total variance (56% for ER positive, 60% for ER negative cancers) than the variance between tumors. Conclusion Intratumoral heterogeneity in Ki67-LI is an ubiquitous phenomenon across various pathological subgroups of breast cancer that may impact assessment of Ki67 levels for clinical decision making, and sheds new light on recommended cut-offs. Citation Format: Focke CM, Decker T, van Diest PJ. Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-03-02.