Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers
Authors
Evans, D. G.Sithambaram, S.
van Veen, E. M.
Burghel, G. J.
Schlecht, H.
Harkness, E. F.
Byers, H.
Ellingford, J. M.
Gandhi, A.
Howell, Sacha J
Howell, A.
Forde, C.
Lalloo, F.
Newman, W. G.
Smith, M. J.
Woodward, E. R.
Affiliation
Division of Evolution and Genomic Science, The University of Manchester School of Health Sciences, Manchester, UKIssue Date
2022
Metadata
Show full item recordAbstract
Purpose: 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.Citation
Evans 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.Journal
Journal of Medical GeneticsDOI
10.1136/jmg-2022-108790PubMed ID
36442995Additional Links
https://dx.doi.org/10.1136/jmg-2022-108790Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1136/jmg-2022-108790