Abstract P1-06-10: Correlative analysis of breast cancer index (BCI) restratification of 21-gene recurrence score (RS) in patients with hormone receptor-positive (HR+), node-negative breast cancer
Authors: Yan F , Master AK , Israel MA , Liu J , Schnabel CA , Hurvitz S , Gadi VK 
Published: February 2018

Abstract
Background: In a cross-stratification analysis performed within the TransATAC cohort, Breast Cancer Index (BCI) and 21-gene Recurrence Score (RS) had a concordance of 58.2% (Sestak et al., Clin Cancer Res, 2016). Restratification by BCI of the low and intermediate RS risk groups led to subgroups with significantly different rates (P &lt; 0.001 and P = 0.003, respectively); in contrast, restratified subgroups created by RS of BCI risk groups did not differ significantly. The objective of this study was to analyze the concordance of BCI and RS test results in HR+, node-negative (LN-) patients tested in the real-world setting and to investigate molecular, clinical, and pathologic correlates within discrepant cases.
Methods: This study utilized a subset of cases from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database which contains clinicopathologic and molecular variables from clinical cases submitted for BCI testing. Clinicopathologic variables, abstracted from pathology reports, were available for a subset of cases. This analysis evaluated cases from LN- patients with available RS data. Concordance was evaluated between BCI Prognostic risk groups (Low, High) and RS risk groups (Low, Intermediate, High based on TAILOR Rx cutpoints [0-10, 11-25, and 26+]). Fisher's Exact tests were used to compare molecular (HoxB13/IL17BR [H/I] endocrine response biomarker and Molecular Grade Index [MGI] proliferation marker) and clinicopathologic (age, grade, size, HER2, Ki67) data in discrepant risk groups.
Results: There were 456 LN- patients included. Median age was 58.0y (range 27.2-84.0y; 73.9% ≥50y); 33.1%/50.1%/16.8% were grade 1/2/3; and 24.0%/59.5%/15.3% were T1ab/T1c/T2. BCI classified 47.8% (n=218) of patients as Low Risk vs 52.2% (n=238) as High Risk. RS classified 17.1% (n=78), 67.1% (n=306), and 15.8% (n=72) of patients as Low, Intermediate, and High Risk, respectively. BCI restratified RS-Low patients as high risk in 17.1% of cases, restratified RS-Intermediate as Low Risk in 48.4% and High Risk in 51.6%, and restratified RS-High as Low risk in 20.8% of cases. In RS-Low patients, only H/I (P=0.0004) and MGI (P=0.047) were significantly correlated with restratification to BCI-High Risk. In RS-Intermediate patients, H/I (P&lt;0.0001), MGI (P&lt;0.0001), grade (P&lt;0.0001), and Ki67 &gt;20% (P=0.0003) were significantly correlated with restratification by BCI to High or Low Risk. In RS-High patients, H/I (P=0.0008), MGI (P&lt;0.0001), grade (P=0.016) were significantly correlated with restratification to Low Risk.
Conclusion: BCI restratified a substantial proportion of patients in each RS risk group. Based on previous studies demonstrating that BCI has improved prognostic ability for assessment of risk of late distant recurrence (Sgroi et al., Lancet Oncol, 2013), these results highlight the clinical utility of BCI within all RS risk groups. The estrogen signaling pathway biomarker H/I and proliferative biomarkers (MGI, grade, Ki67) were associated with restratification by BCI, while age, HER2 status, and tumor size were not.
Citation Format: Yan F, Master AK, Israel MA, Liu J, Schnabel CA, Hurvitz S, Gadi VK. Correlative analysis of breast cancer index (BCI) restratification of 21-gene recurrence score (RS) in patients with hormone receptor-positive (HR+), node-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-10.