Abstract PS4-01-10: Characterizing CCR7 Gene Amplification and Protein Expression in Inflammatory and non-inflammatory Breast Cancer

Abstract Purpose: Inflammatory breast cancer (IBC) is a rare yet exceptionally aggressive subtype that accounts for a disproportionate number of breast cancer deaths. A significant barrier to effective treatment is its ability to invade the lymphatic system and evade immune suppression. Emerging research highlights the potential role of C-C chemokine receptor type 7 (CCR7) in driving tumor progression and modulating immune responses within IBC. Baseline changes in CCR7 gene expression have not been reported in IBC. We investigated CCR7 gene amplification, as well as protein expression and spatial distribution in patient tumors, patient-derived xenografts (PDXs), and IBC cell lines. Methods: PDX characterization of non-IBC models for CCR7 was performed using data from the BCM PDX portal (PDX Insights), and sections from selected PDX were stained for multiplex immunofluorescence (mIF) and imaged with a Nikon Ni-E microscope. Cell lines were subjected to immunoblotting for CCR7, and conditioned media were analyzed by ELISA for CCR7 ligands CCL19 and CCL21. Clinical analysis was performed retrospectively, based on an IRB-approved protocol using genomic data from 18 hormone receptor-positive (HR+) HER2-negative (HER2-) IBC and 24 HR-negative (HR-) HER2- IBC cases which were compared to 150 and 104 subtype-matched non-IBC cases, respectively. Results: CCR7 gene expression did not differ between IBC and non-IBC cases independent of subtype. Four IBC patients in each subtype had gain or amplification of CCR7, while six patients in each subtype had deletion. mRNA expression did not correlate with copy number alterations (CNAs). In triple-negative and HER2+ IBC cell lines, CCR7 protein expression was high. CCR7 ligands were not detected in conditioned media of IBC cell lines. Among non-IBC PDX models characterized from PDX Insights, 9/53 demonstrated gain or amplification of CCR7, while 25/53 demonstrated loss. CCR7 gene expression was not concordant with CNAs; we observed 11% CCR7 gene expression in HR+ HER2- IBC patients and 16% in HR- HER2- IBC patients. mIF analysis of PDX sections from BCM-3104, BCM-3807, and BCM-15029, representing CCR7 amplified/high expression (+/+), non-amplified/high expression (-/+), and non-amplified/low expression (-/-), respectively, revealed significant membranous expression only in the +/+ PDX context with concurrent high expression of podoplanin and ligand CCL21. CCR7 protein and gene expression were roughly correlated, with -/+ expression level being intermediate between -/- and +/+. H&E staining showed tumor necrosis and an increase in inflammatory infiltrate relative to CCR7 gene expression. Conclusion: Patient data suggest that CCR7 CNAs are common in both inflammatory and non-inflammatory breast cancer phenotypes within HR+ HER2- and triple-negative breast cancer subtypes and are not concordant with gene expression overall. In PDX tissues, membranous CCR7 was predominantly found in the amplified PDX context. Additional work is needed to distinguish the impact of membranous versus cytoplasmic CCR7 expression. CCL21 showed greater expression than CCL19, highlighting potential ligand-specific functionality of the CCR7 axis. These characterizations provide important baseline data for further consideration of CCR7 as a target for aggressive breast cancer. Citation Format: S. Shivhare, C. Sanchez, R. Larson, L. Dobrolecki, M. Lewis, J. Chen, M. Sebastian, A. Evdokimova, D. Goncharova, A. Alexander, A. Nasrazadani, R. Layman, B. Lim, V. Valero, A. Lucci, The MDACC Inflammatory Breast Cancer Team, W. Woodward. Characterizing CCR7 Gene Amplification and Protein Expression in Inflammatory and non-inflammatory Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-01-10.