Genetic landscape of interval and screen detected breast cancer.
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Authors
Mills, C
Sud, A
Everall, A
Chubb, D
Lawrence, SED
Kinnersley, B
Cornish, AJ
Bentham, R
Houlston, RS
Sud, A
Everall, A
Chubb, D
Lawrence, SED
Kinnersley, B
Cornish, AJ
Bentham, R
Houlston, RS
Document Type
Journal Article
Date
2024-05-28
Date Accepted
2024-05-02
Abstract
Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project. Compared to SDBCs, IBCs were more likely to be lobular, higher grade, and triple negative. A more aggressive clinical phenotype was reflected in IBCs displaying features of genomic instability including a higher mutation rate and number of chromosomal structural abnormalities, defective homologous recombination and TP53 mutations. We did not however, find evidence to indicate that IBCs are associated with a significantly different immune response. While IBCs do not represent a unique molecular class of invasive breast cancer they exhibit a more aggressive phenotype, which is likely to be a consequence of the timing of tumour initiation. This information is relevant both with respect to treatment as well as informing the screening interval for mammography.
Citation
npj Precision Oncology,
DOI
Source Title
npj Precision Oncology
Publisher
NATURE PORTFOLIO
ISSN
2397-768X
eISSN
2397-768X
Collections
Research Team
Cancer Genomics