Abstract 4744: Clinical validation of a prognostic model integrating Breast Cancer Index (BCI) with tumor size and grade for prediction of late distant recurrence in hormone receptor-positive (HR+) breast cancer with 1-3 positive nodes
Authors: Zhang Yi , Jerevall Piiha-Lotta , Schroeder Brock E. , Ly Amy , Nolan Hannah , Schnabel Catherine A. , Sgroi Dennis C. 
Published: July 2017

Abstract
Background: The Breast Cancer Index (BCI) 11-gene expression signature has been previously demonstrated to significantly predict risk of overall (10y), early (0-5y), and late (≥5y) distant recurrence in patients with HR+, node negative breast cancer. A distinct BCI model that integrated tumor size and grade (BCIN+) was developed and validated for prediction of distant recurrence in HR+ women with 1-3 positive nodes (N1) (Sestak et al., SABCS 2015, P2-08-12; Zhang et al, ASCO 2016, abstract no. 541). The objective of this analysis was to evaluate BCIN+ performance in the subset of patients that were treated with no more than 5 years of adjuvant endocrine therapy.
Methods: The validation study included 402 HR+ N1 patients diagnosed between 1993 to 2007 with ≥5y follow-up and available tumor blocks. Patients treated with ≤5y of endocrine therapy ± chemotherapy (n=276) were included in this analysis. BCIN+ risk scores and categories (low vs high, using a pre-defined cutpoint) were determined blinded to clinical outcome. Kaplan-Meier estimates of overall (0-15y) and late (≥5y) distant recurrence, hazard ratios and 95% CIs were estimated. Multivariate analysis adjusting for standard prognostic factors (age, tumor type, surgery type, PR and HER2 status) was performed using Cox proportional hazards model.
Results: Mean age was 53y. 99% were ER+, 89% PR+, and 14% HER2+. The majority of tumors were T1 (61%) or T2 (34%), and 16%, 53%, and 31% were grade 1, 2, and 3, respectively. 79% of patients were treated with adjuvant chemotherapy. BCIN+ significantly separated patients into low and high risk groups for both overall (P&lt;0.0001) and late (P=0.0067) distant recurrence. For overall distant recurrence, BCIN+ classified 18% of patients into the low risk group. The 15y risk of distant recurrence was 2.1% (95% CI: 0.0-6.0%) in the BCIN+ low risk group vs 36.8% (95% CI: 29.3-43.4%) in the high risk group (HR: 21.88; 95% CI: 3.04-157.32). Of patients that were distant recurrence-free for at least 5y, 22% were classified as BCIN+ low risk. The risk of distant recurrence at year 15 was 2.1% (95% CI: 0.0-6.0%) in the BCIN+ low risk group vs 19.0% (11.6-25.8%) in the high risk group (HR: 9.49; 95% CI: 1.29-69.7).
Conclusions: In this subset analysis from an independent validation study, BCIN+ identified a significant proportion of N1 patients that were associated with a considerably low 15y risk of distant recurrence after ≤5 years of endocrine therapy ± chemotherapy. BCIN+ may provide additional prognostic information to facilitate selection of N+ patients for extended endocrine treatment wherein patients identified as BCIN+ low may be considered adequately treated with adjuvant therapy alone.
Citation Format: Yi Zhang, Piiha-Lotta Jerevall, Brock E. Schroeder, Amy Ly, Hannah Nolan, Catherine A. Schnabel, Dennis C. Sgroi. Clinical validation of a prognostic model integrating Breast Cancer Index (BCI) with tumor size and grade for prediction of late distant recurrence in hormone receptor-positive (HR+) breast cancer with 1-3 positive nodes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4744. doi:10.1158/1538-7445.AM2017-4744