Abstract P5-08-09: Differential patient stratification by the breast cancer index HoxB13/IL17BR ratio vs recurrence score (RS) plus quantitative ER expression in hormone receptor positive, node negative breast cancer
Authors: Naughton MJ , Schroeder BE , Operana TN , Zhang Y , Schnabel CA 
Published: May 2016

Background: Second generation genomic biomarkers for patients with early stage breast cancer are based on integration of proliferative and estrogen signaling-related gene expression, which has led to data applicable in the extended (post-5 year) endocrine therapy setting. The Breast Cancer Index (BCI) assay interrogates these two signaling pathways, significantly stratified patients into high (13.4%) or low (3.5%) risk of late (5-10y) distant recurrence in TransATAC , and includes a gene expression signature (HoxB13/IL17BR, H/I) that predicted benefit from extended endocrine therapy in MA.17. The 21-gene assay has recently been investigated in combination with quantitative estrogen receptor (qER) expression, wherein a subset of approximately 20% of patients with a high recurrence score (RS) and qER above 9.1 had a higher prognostic risk for late distant recurrence (12.6%) than those with Low RS (4.7%) or intermediate RS (4.1%) (Wolmark, ASCO 2014). The objective of this study was to compare patient stratification with H/I and RS+qER.

Methods: Consecutive cases submitted for BCI clinical testing from lymph node-negative breast cancer patients with available RS scores and qER &gt;9.1 abstracted from pathology reports (N=115) were analyzed. Cohen's kappa statistic was used to test agreement between H/I and RS+qER for patient stratification.

Results: No statistically significant agreement was observed between H/I stratification and RS+qER prognostic risk stratification with respect to identifying patients for extended endocrine therapy (Cohen's kappa = -0.002, p = 0.51). H/I identified 36 cases (34%) as High likelihood to benefit from extended endocrine therapy compared to 3 cases (3%) classified as by RS+qER as having high risk of late recurrence (Table). Of the 69 cases (66%) classified as RS+qER Low risk, 19 were identified as High likelihood to benefit from extended endocrine therapy by H/I.

Table Low H/I PredictiveHigh H/I PredictiveTotalRS+qER Low Risk50 (48%)19 (18%)69 (66%)RS+qER Inter Risk17 (16%)16 (15%)33 (31%)RS+qER High Risk2 (2%)1 (1%)3 (3%)Total69 (66%)36 (34%) 

Conclusions: This retrospective analysis of clinical cases shows that H/I and RS+qER identify distinct subsets of patients, and highlights that the underlying biology of risk stratification differs from that of endocrine responsiveness. Comparatively, findings indicate that the H/I identifies additional patients that may be considered for extended endocrine therapy.

Citation Format: Naughton MJ, Schroeder BE, Operana TN, Zhang Y, Schnabel CA. Differential patient stratification by the breast cancer index HoxB13/IL17BR ratio vs recurrence score (RS) plus quantitative ER expression in hormone receptor positive, node negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-09.