Premium
Molecular comparison of interval and screen‐detected breast cancers
Author(s) -
Cheasley Dane,
Li Na,
Rowley Simone M,
Elder Kenneth,
Mann G Bruce,
Loi Sherene,
Savas Peter,
Goode David L,
Kader Tanjina,
Zethoven Magnus,
Semple Tim,
Fox Stephen B,
Pang JiaMin,
Byrne David,
Devereux Lisa,
Nickson Carolyn,
Procopio Pietro,
Lee Grant,
Hughes Siobhan,
Saunders Hugo,
Fujihara Kenji M,
Kuykhoven Keilly,
Connaughton Jacquie,
James Paul A,
Gorringe Kylie L,
Campbell Ian G
Publication year - 2019
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5251
Subject(s) - germline , germline mutation , breast cancer , oncology , cancer , genetic testing , cohort , pathological , medicine , somatic cell , biology , family history , mutation , genetics , gene
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.