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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Interval breast cancer is associated with interferon immune response

Author

  • Emilio Ugalde-Morales
  • Felix Grassmann
  • Keith Humphreys
  • Jingmei Li
  • Mikael Eriksson
  • Nicholas P. Tobin
  • Linda S. Lindström
  • Johan Vallon-Christersson
  • Åke Borg
  • Per Hall
  • Kamila Czene
Show all

Summary, in English

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.

Department/s

  • Breastcancer-genetics
  • LUCC: Lund University Cancer Centre
  • Create Health
  • Familial Breast Cancer

Publishing year

2022

Language

English

Pages

194-205

Publication/Series

European Journal of Cancer

Volume

162

Document type

Journal article

Publisher

Elsevier

Topic

  • Cancer and Oncology

Keywords

  • Interferon immune response
  • Interval breast cancer
  • Mammographic density
  • PAM50 subtypes

Status

Published

Research group

  • Familial Breast Cancer

ISBN/ISSN/Other

  • ISSN: 0959-8049