Molecular and socioeconomic characteristics of inflammatory breast cancer in the Carolina Breast Cancer Study

Abstract Purpose Inflammatory breast cancer (IBC) has been hypothesized to represent a distinct molecular subtype. However, few IBC-specific gene expression patterns have been identified, and previous genomic studies of IBC have been small with limited information on social determinants. Methods We identified 153 IBC cases in the Carolina Breast Cancer Study (total N = 4,739). RNA expression was measured on the NanoString platform ( N = 74 IBC, 2,696 non-IBC) and used to determine molecular subtypes, including PAM50, immune, homologous recombination deficiency (HRD), and P53 status. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of associations between IBC and patient demographic, molecular, and social characteristics using logistic regression, and compared differences in gene expression using ANOVA. Results Women with IBC were associated with Black and under 50 compared to non-IBC. IBC was associated with rural address (OR = 1.53) and poverty (OR = 1.61). Molecularly, IBC was associated with HER2-enriched (OR = 6.14), Luminal B (OR = 2.90), P53 Mutant-like (OR = 1.79), and high HRD (OR = 1.90). Neither adiposity nor immune subtype was significantly associated with IBC. Only six of 219 genes measured were significantly differentially expressed between IBC and non-IBC, including HER2-related (ERBB2, FGFR4, GRB7) and P53-related genes (BTG2, LOC400043, MAP2K4). Conclusion Although not associated with immune subtypes, IBC showed differences in HER2 and P53 pathways. The association of IBC with rurality and poverty underscores the importance of health care access for timely diagnosis and treatment of IBC.