Abstract P2-05-08: Impact of treatment history on prognostic ability of breast cancer index (BCI): Subset analysis from a validation study of patients with hormone receptor-positive (HR+) breast cancer with 1-3 positive nodes
Authors: Y Zhang, P-L Jerevall, BE Schroeder, A Ly, H Nolan, CA Schnabel, DC Sgroi
Journal: Cancer Research (2017)

Abstract Background: A new BCI model integrating tumor size and grade (BCIN+) was specifically developed and validated for prediction of risk of overall (0-15y) and late (5-15y) distant recurrence (DR) in HR+ women with 1-3 positive nodes (N1). The objective of this study was to evaluate the impact of treatment history on the prognostic performance of BCIN+ in a large clinical validation cohort of pre- and post-menopausal HR+, N1 patients. Methods: The validation cohort was comprised of 402 HR+, N1 patients diagnosed at Massachusetts General Hospital between 1993-2007 with at least 5y of follow-up. BCIN+ risk scores were determined and patients stratified into low or high risk categories using a pre-specified cut-point blinded to clinical outcome. Kaplan-Meier estimates of overall (0-15y) and late (5-15y) DR were estimated and the difference was evaluated by log-rank test. Treatment-specific subsets were analyzed based on adjuvant endocrine (tamoxifen [TAM] only vs any history of aromatase inhibitors [AI]), and adjuvant chemotherapy treatment history. Results: Mean age of patients was 53y. 99% were ER+, 91% PR+, and 13% HER2+. The majority of tumors were T1 (62%) or T2 (35%). Adjuvant endocrine treatment included TAM only for 191 (48%) patients and either AI only or a sequence of TAM and an AI in 211 (52%) patients. Most patients received chemotherapy (n=324; 81%). BCIN+ classified 20% and 80% as low and high risk, respectively. In patients treated with TAM only, BCIN+ low and high risk had significantly different 15y rates of DR (95% CI) of 4.0% (0.0-11.4%) vs 41.7% (33.0-49.3%), respectively (p=0.0005). For patients disease-free at year 5, rates of late DR (5-15y) were 4.0% (0.0-11.5%) vs 20.0% (11.4-27.8%), respectively (p=0.04). In patients treated with an AI, BCIN+ low and high risk had significantly different 15y rates of DR of 0% (0.0-0.0%) vs 15.0% (8.1-21.5%), respectively (p=0.006). For patients disease-free at year 5, rates of late DR were 0.0% (0.0-0.0%) vs 12.2% (5.6-18.3%), respectively (p=0.02). There was no statistically significant difference in the prognostic performance of BCIN+ between patients treated with TAM only versus those with treatment including any history of AI (interaction p=0.99). In the subset of patients treated with chemotherapy, BCIN+ classified 19% and 81% of patients as low and high risk with significantly different 15y rates of DR of 1.7% (0.0-4.9%) vs 30.9% (24.4-36.8%), respectively (p&amp;lt;0.0001). For patients disease-free at year 5, rates of late DR were 1.7% (0.0-4.9%) and 16.3% (10.2-21.9%), respectively (p=0.006). Conclusions: In this subset analysis from a validation study of N1 patients, BCIN+ identified a significant proportion with a significantly low risk of late DR. This study confirms the ability of BCIN+ to identify a subset of patients with significantly low risk of recurrence across adjuvant endocrine and chemotherapy treatment backgrounds. 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: Zhang Y, Jerevall P-L, Schroeder BE, Ly A, Nolan H, Schnabel CA, Sgroi DC. Impact of treatment history on prognostic ability of breast cancer index (BCI): Subset analysis from a validation study of patients with hormone receptor-positive (HR+) breast cancer with 1-3 positive nodes [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 P2-05-08.