Clinicogenomic Characterization of Inflammatory Breast Cancer
Year: 2025
Type: article
Study design: Observational Study
Abstract: PURPOSE: Inflammatory breast cancer (IBC) is a rare and clinically distinct form of breast cancer associated with poor outcomes. The biological mechanisms driving IBC remain poorly understood, partly due to limited large-scale genomic studies that directly compare IBC with non-IBC cases. EXPERIMENTAL DESIGN: We conducted a retrospective analysis of 140 patients with IBC (68 primary tumors and 72 metastatic tumors) and 2,317 patients with non-IBC (700 primary tumors, 65 local recurrences, and 1,552 metastases). We compared clinicopathologic features, single-nucleotide variants, copy-number variants, tumor mutational burden, and exploratory survival outcomes between IBC and non-IBC tumors. RESULTS: The most frequent somatic alterations in IBC were detected in TP53 (72%), ERBB2 (32%), PIK3CA (24%), CCND1 (12%), MYC (9%), FGFR1 (8%), and GATA3 (8%). Multivariate logistic regression revealed a significant enrichment of TP53 single-nucleotide variants in IBC, particularly in HER2+ and hormone receptor-positive disease. Tumor mutational burden did not differ between IBC and non-IBC cases. In HER2+ disease, a pathway analysis revealed an enrichment of NOTCH pathway alterations. TP53, CCND1, and RB1 alterations were associated with poor outcomes in IBC. CONCLUSIONS: This study provides a comprehensive resource of somatic alterations in a large cohort of patients with metastatic IBC and non-IBC, highlighting genomic features associated with worse outcomes. Our findings reveal a significant enrichment of TP53 mutations, reinforcing its critical role in IBC pathogenesis. Few other distinct differences in IBC were observed, suggesting further investigations-beyond bulk sequencing of the somatic genome-are required to better understand the biology driving this aggressive disease.
Source: Clinical Cancer Research
Authors: Nolan Priedigkeit, Beth Harrison, Robert Shue, Melissa E. Hughes, Yvonne Li, Alinés Lebrón-Torres, Gregory J. Kirkner, Liam F. Spurr, Marie Claire Remolano, Sarah Strauss, Janet Files, Anne-Marie Feeney, Libby Grant, Ayesha Mohammed-Abreu, Ana Garrido-Castro, Romualdo Barroso-Sousa, Brittany Bychkovsky, Faina Nakhlis, Jennifer R. Bellon, Tari A. King, Eric P. Winer, Neal Lindeman, Bruce E. Johnson, Lynette Sholl, Deborah Dillon, Beth Overmoyer, Sara M. Tolaney, Andrew D. Cherniack, Nancy U. Lin, Filipa Lynce
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1733809635, G4527854474
OpenAlex ID: W4410430439