BMJ
Journal of Medical Genetics
,  volume 59 ,  issue 2 ,  pages 115-121

High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer

D.L. Evans 1, 2, 3, 4, 5
, 
Elke M. van Veen 1, 2, 3
, 
Helen J Byers 1, 2, 3
, 
Sarah J Evans 2, 3, 6, 7
, 
George J. Burghel 1
, 
Emma R. Woodward 1, 2, 3
, 
Elaine F. Harkness 4, 5, 8
, 
Diana M. Eccles 9
, 
Stephanie L Greville Haygate 9
, 
Jamie M. Ellingford 1, 2, 3
, 
Naomi L. Bowers 1
, 
Marta Pereira 1
, 
Andrew J. Wallace 1
, 
Sasha J Howell 3, 4, 5, 10
, 
Anthony Howell 3, 4, 5, 10
, 
Fiona Lalloo 1
, 
William G. Newman 1, 2, 3
, 
Miriam Smith 1, 2, 3
1
 
2
 
3
 
4
 
Prevent Breast Cancer Centre, Wythenshawe Hospital Manchester
5
 
University NHS Foundation Trust
6
 
Department of Histopathology
7
 
8
 
9
 
10
 
Publication type: Journal Article
Publication date: 2021-03-23
BMJ
BMJ
scimago Q1
wos Q2
SJR: 1.620
CiteScore: 7.9
Impact factor: 3.7
ISSN: 00222593, 14686244
Genetics
Genetics (clinical)
Abstract
Background

While the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.

Methods

Sequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.

Results

Testing 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).

Conclusion

The rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

Found 
Found 

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GOST |
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GOST Copy
Evans D. et al. High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer // Journal of Medical Genetics. 2021. Vol. 59. No. 2. pp. 115-121.
GOST all authors (up to 50) Copy
Evans D., van Veen E., Byers H. J., Evans S. J., Burghel G. J., Woodward E., Harkness E. F., Eccles D. M., Greville Haygate S. L., Ellingford J. M., Bowers N. L., Pereira M., Wallace A. J., Howell S. J., Howell A., Lalloo F., Newman W. G., Smith M. High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer // Journal of Medical Genetics. 2021. Vol. 59. No. 2. pp. 115-121.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1136/jmedgenet-2020-107347
UR - https://doi.org/10.1136/jmedgenet-2020-107347
TI - High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer
T2 - Journal of Medical Genetics
AU - Evans, D.L.
AU - van Veen, Elke M.
AU - Byers, Helen J
AU - Evans, Sarah J
AU - Burghel, George J.
AU - Woodward, Emma R.
AU - Harkness, Elaine F.
AU - Eccles, Diana M.
AU - Greville Haygate, Stephanie L
AU - Ellingford, Jamie M.
AU - Bowers, Naomi L.
AU - Pereira, Marta
AU - Wallace, Andrew J.
AU - Howell, Sasha J
AU - Howell, Anthony
AU - Lalloo, Fiona
AU - Newman, William G.
AU - Smith, Miriam
PY - 2021
DA - 2021/03/23
PB - BMJ
SP - 115-121
IS - 2
VL - 59
PMID - 33758026
SN - 0022-2593
SN - 1468-6244
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2021_Evans,
author = {D.L. Evans and Elke M. van Veen and Helen J Byers and Sarah J Evans and George J. Burghel and Emma R. Woodward and Elaine F. Harkness and Diana M. Eccles and Stephanie L Greville Haygate and Jamie M. Ellingford and Naomi L. Bowers and Marta Pereira and Andrew J. Wallace and Sasha J Howell and Anthony Howell and Fiona Lalloo and William G. Newman and Miriam Smith},
title = {High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer},
journal = {Journal of Medical Genetics},
year = {2021},
volume = {59},
publisher = {BMJ},
month = {mar},
url = {https://doi.org/10.1136/jmedgenet-2020-107347},
number = {2},
pages = {115--121},
doi = {10.1136/jmedgenet-2020-107347}
}
MLA
Cite this
MLA Copy
Evans, D.L., et al. “High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer.” Journal of Medical Genetics, vol. 59, no. 2, Mar. 2021, pp. 115-121. https://doi.org/10.1136/jmedgenet-2020-107347.