Abstract P2-05-18: Correlation of breast cancer index (BCI) risk classification with tumor grade and Ki-67 in a large series of patients with early-stage, ER+ breast cancer
Authors: H Soliman, BE Schroeder, Y Zhang, AM Magliocco, CA Schnabel
Journal: Cancer Research (2017)

Abstract Background: Breast Cancer Index (BCI) is a gene expression-based test that integrates biomarker panels of both proliferation (molecular grade index, MGI), and endocrine response (HoxB13/IL17BR). BCI has been validated as a significant and independent prognostic factor both for risk of overall (0-10y) and late (&amp;gt;5y) distant recurrence, and is predictive of extended endocrine benefit in patients with early-stage, ER+ breast cancer. In this study, correlative analyses of risk stratification by BCI and MGI versus tumor grade or Ki67 were assessed to characterize their relationship to other markers of proliferation. Methods: Retrospective analysis of consecutive cases (N=1359) from node negative early-stage breast cancer patients submitted for clinical testing with BCI were analyzed. Median age at diagnosis was 58 years, 57% and 6% were HER2 negative and positive, respectively, with 37% unknown status. Tumor grade and Ki67 information was abstracted from pathology reports, and was available for 1335 and 372 cases, respectively. 29%, 52% and 17% of patients had grade 1, 2 and 3 tumors, respectively, with 2% having unknown grade. Tumor sizes were 26% (≤ 1cm), 48% (&amp;gt;1 - ≤ 2cm), 23% (&amp;gt;2 - ≤ 5cm), 2% (≥ 5cm) and 1% were unknown. Ki67 categories were based on 10% and 20% IHC expression levels into low, intermediate and high groups. Statistical methods included Pearson correlation between BCI/MGI versus Ki67 as continuous variables &amp; coefficient of determination derived from the analysis of variance (ANOVA) model between continuous BCI/MGI versus tumor grade. Chi-square test assessed the significance of concordance between BCI, MGI risk groups to tumor grade and Ki67 groups. Results: As continuous variables, BCI and MGI correlated weakly with tumor grade (coefficient of determination= 0.26 and 0.22, respectively) and Ki67 (r2 = 0.35 and 0.33, respectively). Although statistically significant concordance was demonstrated between BCI/tumor grade, MGI/tumor grade, BCI/Ki67, MGI/Ki67 categories (p&amp;lt;0.0001 for all, Tables 1 &amp; 2), discordance between BCI versus tumor grade or Ki67 was 51% and 45%, respectively. In particular, BCI classified 4% of well differentiated tumors as high-risk and 18% of poorly differentiated tumors as low-risk. Similarly, BCI classified 4% of low Ki67 patients as high risk and 28% of high Ki67 patients as low risk. Table 1: BCI risk classification vs tumor grade Grade 1Grade 2Grade 3BCI Low Risk30536542BCI Intermediate Risk6921656BCI High Risk15130137 Table 2: BCI risk classification vs Ki67 Ki67 LowKi67 IntermediateKi67 HighBCI Low Risk1094740BCI Intermediate Risk213645BCI High Risk6860 Conclusions: Data from this large retrospective analysis show that correlation of BCI and its mitogenic panel, MGI, to tumor grade and Ki67 are moderate to weak. These findings indicate that BCI and MGI are capturing distinct information related to tumor proliferative status compared with tumor grade and Ki67. Citation Format: Soliman H, Schroeder BE, Zhang Y, Magliocco AM, Schnabel CA. Correlation of breast cancer index (BCI) risk classification with tumor grade and Ki-67 in a large series of patients with early-stage, ER+ breast cancer [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 P2-05-18.