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Interval breast cancer is associated with interferon immune response

Ugalde-Morales, Emilio ; Grassmann, Felix ; Humphreys, Keith LU ; Li, Jingmei ; Eriksson, Mikael ; Tobin, Nicholas P. LU ; Lindström, Linda S. ; Vallon-Christersson, Johan LU orcid ; Borg, Åke LU and Hall, Per , et al. (2022) In European Journal of Cancer 162. p.194-205
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Interferon immune response, Interval breast cancer, Mammographic density, PAM50 subtypes
in
European Journal of Cancer
volume
162
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:85122538242
  • pmid:35026490
ISSN
0959-8049
DOI
10.1016/j.ejca.2021.12.003
language
English
LU publication?
yes
id
a8416386-ad1a-470a-87dc-aa039af2033a
date added to LUP
2022-02-28 11:50:26
date last changed
2024-06-08 14:49:18
@article{a8416386-ad1a-470a-87dc-aa039af2033a,
  abstract     = {{<p>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 &lt;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 &lt; 0.05, fold-change &gt; 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 &lt; 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.</p>}},
  author       = {{Ugalde-Morales, Emilio and Grassmann, Felix and Humphreys, Keith and Li, Jingmei and Eriksson, Mikael and Tobin, Nicholas P. and Lindström, Linda S. and Vallon-Christersson, Johan and Borg, Åke and Hall, Per and Czene, Kamila}},
  issn         = {{0959-8049}},
  keywords     = {{Interferon immune response; Interval breast cancer; Mammographic density; PAM50 subtypes}},
  language     = {{eng}},
  pages        = {{194--205}},
  publisher    = {{Elsevier}},
  series       = {{European Journal of Cancer}},
  title        = {{Interval breast cancer is associated with interferon immune response}},
  url          = {{http://dx.doi.org/10.1016/j.ejca.2021.12.003}},
  doi          = {{10.1016/j.ejca.2021.12.003}},
  volume       = {{162}},
  year         = {{2022}},
}