Abstract A086: Molecular and socioeconomic characteristics of inflammatory breast cancer in the Carolina breast cancer study

Abstract Inflammatory breast cancer (IBC) has been hypothesized to represent a distinct molecular subtype of breast cancer. However, while IBC is considered a distinct clinicopathological entity, attempts to elucidate an IBC-specific gene signature have been challenging and inconclusive. Studies linking IBC to specific genomic pathways have been hampered by small sample sizes, and many previous studies with molecular data have also lacked information on demographics and access to care. This study examined IBC using the Carolina Breast Cancer Study (CBCS), a population-based cohort comprising 4,739 invasive breast cancer samples from patients across three phases (1993–2013). African American (AA) and younger women (<50 years old) were oversampled in CBCS. Demographic, clinical, molecular, and socioeconomic data were analyzed for both IBC and non-IBC breast cancer samples in CBCS. In CBCS, 153 women had IBC (3%) based on medical records. Women diagnosed with IBC were more likely to be AA (63%) and <50 years old (60%) compared to non-IBC cases (47% and 51%, respectively). Obesity and high waist-to-hip ratio were not significantly associated with IBC after adjustment for age and race. IBC showed a strong association with rural residence (79% vs. 15% in non-IBC) and poverty (46% vs. 33% in non-IBC). IBC was strongly associated with PAM50 subtypes, showing higher frequency of HER2-enriched (31% vs. 11% in non-IBC) and Luminal B (24% vs. 19% in non-IBC), but less frequently Luminal A (12% vs. 30% in non-IBC) and Basal-like (23% vs. 29% in non-IBC), mutant-like P53 (64% vs. 46% in non-IBC), and high homologous recombination deficiency (64% vs. 44% in non-IBC). Global immune subtypes (adaptive-enriched, innate-enriched, immune-quiet determined from bulk RNA expression) showed no association with IBC. Only six genes from the 219 genes measured across all specimens were significantly differentially expressed, including HER2-associated genes (ERBB2, FGFR4, GRB7) and P53-associated genes (BTG2, LOC400043, MAP2K4). Principal component analysis based on expression of these six genes did not strongly distinguish IBC from non-IBC. Overall, the association with intrinsic PAM50 subtypes but not immune response and the small number of differentially expressed genes suggest that IBC is not a distinct defined molecular subtype separate from non-IBC. However, IBC is a challenging diagnosis with variations in clinical presentation. For the field, common diagnostic criteria are being defined and validated clinically and so the inclusion of larger numbers of IBC samples in future molecular studies that have been clearly diagnosed as definite IBC may help in identifying unique IBC molecular/genetic signatures. Our findings that IBC is strongly associated with rurality and poverty underscores the importance of health care access for timely diagnosis and treatment of IBC. Citation Format: Qichen Wang, Sarah C. Van Alsten, Xiaojia Ji, Esraa Salim, Nicole Salazar, John E. Scott, Xiaohe Yang, Rob U. Onyenwoke, Melissa A. Troester, Kevin P. Williams. Molecular and socioeconomic characteristics of inflammatory breast cancer in the Carolina breast cancer study [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A086.