Abstract P2-08-42: Use of breast cancer index to analyze tumor proliferation and endocrine responsiveness in genomic intermediate risk patients
Authors: Yan F , Master AK , Israel MA , Liu J , Zhang Y , Schnabel CA , Gadi VK 
Published: May 2019

Background: Breast Cancer Index (BCI) is a genomic assay that stratifies patients (pts) for cumulative 10-year and late (post–5-year) risk of distant recurrence and predicts the likelihood of extended endocrine therapy (EET) benefit based on the algorithmic analysis of gene expression from two functional gene cassettes: 1) The Molecular Grade Index (MGI), which contains 5 proliferation genes and 2) The HoxB13/IL17BR (H/I) ratio, an endocrine response biomarker. BCI more precisely resolves genomic intermediate risk patients into low- and high-risk groups (Sestak, Clin Cancer Res 2016) and adds significant prognostic data beyond clinical features (ie, clinical treatment score; Sestak, JAMA Oncol 2017) by interrogating different aspects of tumor biology such as proliferation and endocrine response. The objective of this study was to measure tumor proliferation and endocrine responsiveness using MGI and H/I respectively and evaluate their correlation with age in genomic intermediate risk pts.

Methods: This study utilized a subset of cases from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database that contains clinicopathologic and molecular variables from clinical cases submitted for BCI testing. Genomic intermediate risk cases were defined as LN-, HER2- (or HER2 status unknown) with 21-gene recurrence scores (RS) of 11 to 25 using cut-points from the TAILORx study. Quantitative scores for MGI and H/I were derived by algorithmic analysis of BCI gene expression. Age groups (&lt;50y and ≥51y) were determined using the date of diagnosis. MGI and H/I were evaluated in two different genomic intermediate risk groups: RS 11-15 and RS 16-25. Pearson correlation coefficients were used to determine the correlation between MGI, BCI, H/I, and genomic intermediate risk scores for patients &lt;50y and ≥51y.

Results: Of the 441 pts with RS and BCI results, 303 (69%) with genomic intermediate risk were analyzed. The median MGI score in pts ≥51y was higher in the RS 16-25 group compared to RS 11-15, but there was no difference in MGI score between the two genomic intermediate RS risk groups for pts &lt;50y. In contrast to MGI, median H/I was higher in the RS 16-25 group irrespective of age, with 37% of pts &lt;50y and 41% of pts ≥51y having tumors predicted as more likely to benefit from EET using validated cut-points for H/I. There was no significant correlation between tumor proliferation (MGI: r=0.166) or endocrine responsiveness (H/I: r=0.244) with genomic intermediate-risk RS 11-25 group.

Conclusion: These data, which show variations in tumor proliferation and endocrine signaling based on age and genomic intermediate risk group, highlight the importance of measuring different features of tumor biology for risk classification and prediction of therapy response. The absence of correlations between tumor proliferation and genomic intermediate risk and age, and between estrogen signaling and genomic intermediate risk and age, suggests that assays such as BCI that combine distinct aspects of tumor biology for prognosticating risk of recurrence and prediction of benefit from endocrine therapy provide additional value for individualizing the management of patients with early-stage ER+ breast cancer.

Citation Format: Yan F, Master AK, Israel MA, Liu J, Zhang Y, Schnabel CA, Gadi VK. Use of breast cancer index to analyze tumor proliferation and endocrine responsiveness in genomic intermediate risk patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-42.