Background: There is increasing evidence that the presence of a host inflammatory response to breast cancer may influence outcomes. Utilizing inflammation scores on the histology of breast cancer samples submitted for comprehensive molecular analyses for The Cancer Genome Atlas (TCGA), we provide an updated look at associations between the presence of host inflammation and breast cancer molecular and pathologic features.
Design: Experts in breast pathology reviewed the digital slides of breast cancer samples submitted for comprehensive molecular profiling to the TCGA and scored each case for the level of inflammation present (high/moderate vs mild/minimal). We tested pairwise associations between host inflammation and molecular subtypes (DNA copy-number, RNA expression, RPPA defined subtypes, miRNA subtypes, methylation subtypes) and pathological features by performing Chi-Square analyses. Multiple hypothesis testing correction was performed using the Bonferroni method.
Results: 598 breast cancer cases with TCGA molecular profiling data were scored by the expert breast pathologists for morphological features (including inflammation). 195 (33%) of these were scored as high/moderate inflammation. Cases with inflammation had a significantly higher rate of TP53 mutations (p = 9.0e-8) with 64 of 118 (54.2%) p53 mutant cases with inflammation. Inflammation was also significantly associated with PAM50 molecular subtypes (p = 2.2e-11), with the greatest enrichment among basal-like (64.5% of 70 basal-like cases had inflammation) and the greatest depletion among Luminal A (18.1% of 166 Luminal A cases had inflammation). Cases with inflammation were significantly less likely to be lobular (p = 1.5e-7), had less tubule formation (p = 0.0006), increased mitoses (p <2.2 e-16), increased nuclear pleomorphism (p = 2.9e-15), and increased necrosis (p = 2.9e-14).
Conclusions: There are strong associations between breast cancer molecular and pathological features and the host inflammatory response.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-05-06.