Interval breast cancer is associated with interferon immune response
(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.
(Less)
- author
- organization
- publishing date
- 2022
- 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 <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.</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}}, }