LAUSR

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 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