Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers

D Gareth Evans; Sivagamy Sithambaram; Elke M van Veen; George J  Burghel; Helene Schlecht; Elaine Harkness; Helen J.  Byers; Jamie Ellingford; Ashu Gandhi; Sacha J. Howell; Tony Howell; Claire Forde; Fiona  Lalloo; William Newman; Miriam J Smith; Emma Woodward

doi:10.1136/jmg-2022-108790

Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers

D Gareth Evans, Sivagamy Sithambaram, Elke M van Veen, George J Burghel, Helene Schlecht, Elaine Harkness, Helen J. Byers , Jamie Ellingford, Ashu Gandhi, Sacha J. Howell, Tony Howell, Claire Forde, Fiona Lalloo, William Newman, Miriam J Smith, Emma Woodward

Central Manchester University Hospitals NHS Foundation Trust

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Abstract

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
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.

Original language	English
Journal	Journal of Medical Genetics
DOIs	https://doi.org/10.1136/jmg-2022-108790
Publication status	Published - 28 Nov 2022

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Manchester Cancer Research Centre

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10.1136/jmg-2022-108790

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Evans, D. G., Sithambaram, S., van Veen, E. M., Burghel, G. J., Schlecht, H., Harkness, E., Byers , H. J., Ellingford, J., Gandhi, A., Howell, S. J., Howell, T., Forde, C., Lalloo, F., Newman, W., Smith, M. J., & Woodward, E. (2022). Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers. Journal of Medical Genetics. https://doi.org/10.1136/jmg-2022-108790

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title = "Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers",

abstract = "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 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.",

author = "Evans, {D Gareth} and Sivagamy Sithambaram and {van Veen}, {Elke M} and Burghel, {George J} and Helene Schlecht and Elaine Harkness and Byers, {Helen J.} and Jamie Ellingford and Ashu Gandhi and Howell, {Sacha J.} and Tony Howell and Claire Forde and Fiona Lalloo and William Newman and Smith, {Miriam J} and Emma Woodward",

year = "2022",

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day = "28",

doi = "10.1136/jmg-2022-108790",

language = "English",

journal = "Journal of Medical Genetics",

issn = "1468-6244",

publisher = "BMJ ",

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Evans, DG, Sithambaram, S, van Veen, EM, Burghel, GJ, Schlecht, H, Harkness, E, Byers , HJ, Ellingford, J, Gandhi, A, Howell, SJ, Howell, T, Forde, C, Lalloo, F, Newman, W , Smith, MJ & Woodward, E 2022, 'Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers', Journal of Medical Genetics. https://doi.org/10.1136/jmg-2022-108790

TY - JOUR

T1 - Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers

AU - Evans, D Gareth

AU - Sithambaram, Sivagamy

AU - van Veen, Elke M

AU - Burghel, George J

AU - Schlecht, Helene

AU - Harkness, Elaine

AU - Byers , Helen J.

AU - Ellingford, Jamie

AU - Gandhi, Ashu

AU - Howell, Sacha J.

AU - Howell, Tony

AU - Forde, Claire

AU - Lalloo, Fiona

AU - Newman, William

AU - Smith, Miriam J

AU - Woodward, Emma

PY - 2022/11/28

Y1 - 2022/11/28

N2 - 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 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.

AB - 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 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.

U2 - 10.1136/jmg-2022-108790

DO - 10.1136/jmg-2022-108790

M3 - Article

SN - 1468-6244

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

ER -

Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers

Abstract

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