Abstract 3903: Multi-omics and histological assessment to identify patient derived xenograft models of invasive lobular carcinoma

Abstract Breast cancer is a heterogeneous disease with various histological subtypes. Invasive Lobular Cancer (ILC) is the most common special subtype, accounting for 10-15% of all breast cancers. The pathognomonic feature of ILC is the loss of E-cadherin (CDH1), which leads to a unique single-file growth pattern of discohesive ILC cells. Although ILCs show better prognostic factors than No Special Type (NST), patients with ILC have worse long-term outcomes, which is not well understood. ILC has historically been understudied, in part due to the lack of appropriate research models. Since ILC affects "only" 10-15% of all breast cancers, most models have been generated from the more frequent subtype, NST. In this study, we characterized Patient-Derived Xenograft (PDX) models for Invasive Lobular Cancer (ILC) research. We collaborated with Champions Oncology and utilized the genomic data from their LUMIN portal to perform genomic characterization of PDX models. We identified potential ILC PDX models based on CDH1 mutation, low E-cadherin mRNA expression, or clinical annotation of ILC. We analyzed whole-exome sequencing (WES) and RNAseq data on the LUMIN portal to characterize these models. We also performed Immunohistochemistry (IHC) analysis for E-Cadherin, p120, ER, PR, and Her2 to further assess the PDX models. Our study characterized a total of 10 PDX models and identified 7 ILC models and 3 NST models. We showed that the identified ILC PDX models exhibited lower levels of CDH1 mRNA expression compared to NST, which is consistent with the characteristics of ILC. We also found that the top gene alterations in ILC PDX models included P53, CDH1, PIK3CA, FOXA1, and PTEN. The frequency and type of alterations varied between ILC and NST PDXs. Our study provides valuable tools for studying ILC biology and testing targeted therapies. The identification of potential ILC PDX models could provide insights into the molecular characteristics of ILC and provide tools for research for the development of new treatment strategies. Citation Format: Jagmohan Hooda, Jennifer M. Atkinson, Osama Shah, Megan Yates, Daniel D. Brown, Morgan DeBerry, Rohit Bhargava, Paolo Schiavini, Stefano Cairo, Mara Gilardi, Marianna Zipeto, Steffi Oesterreich, Adrian V. Lee. Multi-omics and histological assessment to identify patient derived xenograft models of invasive lobular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3903.