Breast cancer index and prognostic performance in invasive lobular breast cancer

Background: Invasive lobular carcinoma (ILC) has distinct clinical, histologic, molecular, and biological characteristics. Dyscohesive cells infiltrating the mammary stroma, lack of E-cadherin expression, mutations in the PIK3CA pathway and lower incidence of GATA3 mutations are hallmarks of these tumors. As a result of these molecular features, tumor biology is of key importance in determining prognosis and treatment approaches for ILC. The Breast Cancer Index (BCI) is a gene expression signature validated as a significant and independent prognostic factor both for risk of overall (0-10 years) and late (5-10 years post-diagnosis) distant recurrence, and is predictive of extended endocrine benefit in patients with early-stage, HR+ breast cancer. The objective of the current study is to examine BCI prognostic risk stratification and potential clinical utility specifically in ILC. Methods: In this multi-institutional, prospectively defined retrospective study, FFPE tumor samples from 356 HR+ stage I-III N0 and N+ ILC patients diagnosed between 1997-2011 were collected. Genomic risk stratification was performed using BCI-prognostic models (N0: gene expression alone; N+: gene expression plus tumor size and grade) using previously validated assay cut-points. Prognostic performance for 10-year and late DR risk was estimated using Kaplan-Meier analysis and the difference was evaluated by log-rank test and Cox proportional hazards regression. Results: Results were generated on 311 evaluable patients (99% ER+, T1 52%, 42% N+, 66% grade II) with 10 years of median follow-up. BCI significantly stratified ILC patients into three prognostic risk groups based on 10-year risk of DR (p Citation Format: Tal Sella, Raquel Nunes, Kai Treuner, Jennifer Atkinson, Jenna Wong, Yi Zhang, Pedro Exman, David Dabbs, Andrea Richardson, Catherine Schnabel, Dennis Sgroi, Steffi Oesterreich, Ashley Cimino-Mathews, Otto Metzger. Breast cancer index and prognostic performance in invasive lobular breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-03.