P1-02-05: Invasive Lobular Carcinoma – A Luminal Breast Cancer Histotype Enriched for Epithelial-to-Mesenchymal Transition Features.

Abstract

Abstract Background: Invasive lobular carcinoma (ILC) represent the second most common breast cancer (BC) histotype, but little information is available about its molecular features. We sought to perform a comprehensive molecular classification of ILC and to investigate the molecular features that can differentiate ILC from invasive ductal carcinoma (IDC). Methods: A consecutive series of 174 ILC tumors from three different centers with mininum 5-year follow-up was selected. Gene expression data were generated using Affymetrix U133 Plus 2.0 arrays. Data were analyzed by using frozen robust multiarray analysis (Matthew et al. 2009). ILC tumors were classified into BC molecular subtypes using the PAM50 classifier. Invasive Disease Free Survival (IDFS) was defined as the interval between the date of surgery and the date of any invasive recurrence or death. Multivariate analyses for 10-y IDFS containing classical clinico-pathologic characteristics were performed for different gene signatures, which were scaled so that 2.5 and 97.5% percentiles equal −1 and 1. A cohort of 90 IDC tumor samples, normalised with the same method, was used to compare expression data between ILC and IDC. Results: ILCs were mainly characterized as luminal A (LA: 76%, n=133) and luminal B (LB:; 20%, n=34) followed by a minority of HER2−positive (2%, n=3), basal (1%, n=2) and normal-like (1%, n=2) based on Perou's classification. LB had inferior 10-y IDFS than LA in univariate cox regression analysis (HR = 1.99, 95% CI, 1.08−3.67, p=0.026). The EMT gene module was significantly higher expressed in ILC as compared to IDC (p < 0.001). Adjusted hazard ratios (HR) for different gene modules investigated are detailed in the table below. Conclusions: ILC is mainly composed of luminal tumors and a minority of HER2−positive tumors. Similarly to IDC, proliferation remains a statistically significant prognostic factor for ILC. ILC tumors were enriched with an EMT phenotype, which is not observed among IDC luminals. Of interest IGF signaling, which is known to be associated with poor prognosis in ER-positive BC, added prognostic value in this population which may open new therapeutics avenues for ILC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-05.