Abstract P2-05-14: Prognostic impact of genomic risk stratification with breast cancer index in patients with clinically low risk, hormone receptor-positive, node-negative, T1 breast cancer

Abstract Background: Tumor size and nodal status are prognostic for risk of both early and late disease recurrence in patients with early stage, HR+ breast cancer, and are incorporated into both adjuvant chemotherapy and extended endocrine therapy treatment decisions. In a recent EBCTCG meta-analysis of over 46,000 patients [Pan H, et al. J Clin Oncol 34, 2016 (suppl; abstr 505)], risk of late distant recurrence was assessed in patient subsets based on nodal status and tumor size. Patients with T1N0 disease who were treated with 5 years endocrine therapy had a good overall prognosis, with 4%, 9%, and 14% risk of distant recurrence from years 5-10, 5-15, and 5-20, respectively. Breast Cancer Index (BCI) has been validated as prognostic biomarker for risk of both early and late distant recurrence in multiple randomized trial cohorts. The aim of this analysis was to assess distant recurrence (DR) risk stratification with BCI in patients with clinically low-risk T1N0 tumors. Methods: Primary tumor samples from the subset of patients with T1N0 disease from 2 independent validation cohorts of HR+ breast cancer patients were examined [Stockholm randomized controlled trial (N=259) and a retrospective multi-institutional cohort (N=237)]. Patients in the Stockholm RCT cohort were treated with adjuvant tamoxifen only; patients in the multi-institutional cohort were treated with adjuvant tamoxifen +/- chemotherapy (20.3%). No patients received extended endocrine therapy. Kaplan-Meier analysis was used to assess the risk of DR within distinct BCI risk groups. Time dependent analysis was performed by combining BCI Low and Intermediate risk groups for risk of early recurrence (0-5y), and BCI Intermediate and High risk groups for risk of late recurrence (>5y). Results: In the Stockholm cohort, BCI identified 13% of T1N0 patients as high risk for relapse within the first 5y, and these patients had a significantly reduced distant recurrence-free survival (DRFS, 85.3%) compared to BCI Low Risk patients (97.7%; P=0.0004). In patients disease-free at year 5, BCI identified 32% of patients as high risk for late recurrence; these patients had significantly lower DRFS (86.7%) between years 5-15 compared to BCI low risk patients (95.4%; P=0.0263). In the multi-institutional cohort, 22% of T1N0 patients were identified by BCI as high risk for relapse within the first 5y, and these patients had a significantly reduced DRFS (77.3%) compared to BCI low risk patients (96.2%; P<0.0001). In patients disease-free at year 5, 36% of patients were identified by BCI as high risk for late recurrence, with significantly lower DRFS (89.6%) between years 5-10 compared to BCI Low Risk patients (98.4%; P=0.008). Conclusions: HR+ Patients with favorable clinical features (T1N0) have a good overall prognosis. However, results of this study demonstrated that adding molecular resolution on tumor biology with BCI identified a significant subset of women with higher risk of both early and late distant recurrence; findings support consideration of genomic classification in T1N0 patients to identify additional candidates for adjuvant chemotherapy and/or extended endocrine therapy, respectively. Citation Format: Schroeder BE, Zhang Y, Stal O, Fornander T, Brufsky A, Sgroi DC, Schnabel CA. Prognostic impact of genomic risk stratification with breast cancer index in patients with clinically low risk, hormone receptor-positive, node-negative, T1 breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-14.