Molecular comparison of interval and screen-detected breast cancers.

Adult Aged Aged, 80 and over Biomarkers, Tumor / genetics Breast Neoplasms / diagnostic imaging DNA Copy Number Variations Early Detection of Cancer / methods Female Gene Dosage Genetic Predisposition to Disease Germ-Line Mutation Humans Mammography Middle Aged Mutation Rate Phenotype Predictive Value of Tests Prognosis Prospective Studies Registries Victoria

breast cancer copy number alteration genetic predisposition genomics interval breast cancer mammographic density mammographic screening next generation sequencing screen-detected breast cancer somatic mutation

Journal

The Journal of pathology

ISSN: 1096-9896

Titre abrégé: J Pathol

Pays: England

ID NLM: 0204634

Informations de publication

Date de publication:
06 2019

Historique:

received: 27 11 2018

revised: 15 01 2019

accepted: 30 01 2019

pubmed: 13 2 2019

medline: 14 4 2020

entrez: 13 2 2019

Statut: ppublish

Résumé

Breast cancer (BC) diagnosed after a negative mammogram but prior to the next screening episode is termed an 'interval BC' (IBC). Understanding the molecular differences between IBC and screen-detected BCs (SDBC) could improve mammographic screening and management options. Therefore, we assessed both germline and somatic genomic aberrations in a prospective cohort. Utilising the Lifepool cohort of >54 000 women attending mammographic screening programs, 930 BC cases with screening status were identified (726 SDBC and 204 IBC). Clinico-pathological and family history information were recorded. Germline and tumour DNA were collected where available and sequenced for BC predisposition and driver gene mutations. Compared to SDBC, IBCs were significantly associated with a younger age at diagnosis and tumour characteristics associated with worse prognosis. Germline DNA assessment of BC cases that developed post-enrolment (276 SDBCs and 77 IBCs) for pathogenic mutations in 12 hereditary BC predisposition genes identified 8 carriers (2.27%). The germline mutation frequency was higher in IBC versus SDBC, although not statistically significant (3.90% versus 1.81%, p = 0.174). Comparing somatic genetic features of IBC and SDBC matched for grade, histological subtype and hormone receptor revealed no significant differences, with the exception of higher homologous recombination deficiency scores in IBC, and copy number changes on chromosome Xq in triple negative SDBCs. Our data demonstrates that while IBCs are clinically more aggressive than SDBC, when matched for confounding clinico-pathological features they do not represent a unique molecular class of invasive BC, but could be a consequence of timing of tumour initiation and mammographic screening. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Identifiants

DOI: 10.1002/path.5251 PMID: 30746706

pubmed: 30746706

doi: 10.1002/path.5251

doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

243-252