Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers
AuthorsEvans, D. G.
van Veen, E. M.
Burghel, G. J.
Harkness, E. F.
Ellingford, J. M.
Howell, Sacha J
Newman, W. G.
Smith, M. J.
Woodward, E. R.
AffiliationDivision of Evolution and Genomic Science, The University of Manchester School of Health Sciences, Manchester, UK
MetadataShow full item record
AbstractPurpose: To investigate frequency of germline pathogenic variants (PVs) in women with ductal carcinoma in situ (DCIS) and grade 1 invasive breast cancer (G1BC). Methods: We undertook BRCA1/2 analysis in 311 women with DCIS and 392 with G1BC and extended panel testing (non-BRCA1/2) in 176/311 with DCIS and 156/392 with G1BC. We investigated PV detection by age at diagnosis, Manchester Score (MS), DCIS grade and receptor status. Results: 30/311 (9.6%) with DCIS and 16/392 with G1BC (4.1%) had a BRCA1/2 PV (p=0.003), and 24/176-(13.6%) and 7/156-(4.5%), respectively, a non-BRCA1/2 PV (p=0.004). Increasing MS was associated with increased likelihood of BRCA1/2 PV in both DCIS and G1BC, although the 10% threshold was not predictive for G1GB. 13/32 (40.6%) DCIS and 0/17 with G1BC <40 years had a non-BRCA1/2 PV (p<0.001). 0/16 DCIS G1 had a PV. For G2 and G3 DCIS, PV rates were 10/98 (BRCA1/2) and 9/90 (non-BRCA1/2), and 8/47 (BRCA1/2) and 8/45 (non-BRCA1/2), respectively. 6/9 BRCA1 and 3/26 BRCA2-associated DCIS were oestrogen receptor negative-(p=0.003). G1BC population testing showed no increased PV rate (OR=1.16, 95% CI 0.28 to 4.80). Conclusion: DCIS is more likely to be associated with both BRCA1/2 and non-BRCA1/2 PVs than G1BC. Extended panel testing ought to be offered in young-onset DCIS where PV detection rates are highest.
CitationEvans DG, Sithambaram S, van Veen EM, Burghel GJ, Schlecht H, Harkness EF, et al. Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers. Journal of medical genetics. 2022 Nov 28. PubMed PMID: 36442995. Epub 2022/11/29. eng.
JournalJournal of Medical Genetics
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