Next-generation targeted sequencing (NGTS) investigating CDK4 as a prognostic driver in pure invasive lobular breast carcinoma (ILC): Preliminary results in early-stage patients (pts) stratified according to a validated clinico-pathological model.

542Background: The aim of this analysis was to investigate the distribution of molecular abnormalities and their potential role as therapeutic targets (with particular regard to CDK4/6 alterations) in resected ILC pts, grouped according to prognosis. Methods: Clinico-pathological multi-center data of early-stage pure ILC pts were correlated to disease-free survival (DFS). A continuous score was derived according to multivariate Hazard Ratios, to develop a 3-class model. The model was validated in an external pts’ cohort. Mutational and Copy Number Variation (CNV) analyses by NGTS, including 26 genes, were performed for pts at Poor and Good Prognosis (PP/GP). Quantitative-PCR analysis was applied for CNV validation; IHC for CDK6 was accomplished. Fisher’s exact test and Peto Odds Ratio (OR) were adopted for comparison. Results: Data from 773 pts (Training/Validation Set [TS/VS]: 491/282) were gathered. At multivariate analysis, T-size and N-status were independent predictors for DFS. A significant differen...