Interval breast cancer is associated with interferon immune response.
Eur J Cancer
; 162: 194-205, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-35026490
ABSTRACT
BACKGROUND:
The aggressive nature of breast cancers detected between planned mammographic screens, so-called interval cancers, remains elusive. Here, we aim to characterise underlying molecular features of interval cancer.METHODS:
From 672 patients with invasive breast cancer, we analysed gene expression differences between 90 'true' interval cancer cases (i.e. women with low-dense breasts defined as per cent mammographic density <25%) and 310 screen-detected tumours while accounting for PAM50 subtypes and thus overall tumour aggressiveness. We computed an interval cancer gene expression profile (IC-Gx) in a total of 2270 breast tumours (regardless of interval cancer status) and tested for association with expression-based immune subtypes in breast cancer. In addition, we investigated the contribution of inherited and somatic genetic variants in distinct features of interval cancer.RESULTS:
We identified 8331 genes nominally associated with interval cancer (P-value < 0.05, fold-change > 1.5). Gene set enrichment analysis showed immune-related pathways as key processes altered in interval cancer. Our IC-Gx, based on 47 genes with the strongest associations (false discovery rate < 0.05), was found to be associated mainly with immune subtypes involving interferon response. We isolated an interaction network of interval cancer and interferon genes for which a significant load of somatic and germline variants in class I interferon genes was observed.CONCLUSION:
We identified novel molecular features of interval breast cancer highlighting interferon pathways as a potential target for prevention or treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2022
Tipo de documento:
Article