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

  • External authors:
  • Elke Van Veen
  • Sarah Evans
  • George Burghel
  • Emma Woodward
  • Diana M Eccles
  • Stephanie Greville-Heygate
  • Naomi L Bowers
  • Marta Pereira
  • Andrew J Wallace
  • Tony Howell
  • Fiona Lalloo
  • William Newman
  • Miriam J Smith

Standard

High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer. / Evans, D Gareth; Van Veen, Elke; Byers, Helen; Evans, Sarah; Burghel, George; Woodward, Emma; Harkness, Elaine; Eccles, Diana M; Greville-Heygate, Stephanie; Ellingford, Jamie; Bowers, Naomi L; Pereira, Marta; Wallace, Andrew J; Howell, Sacha; Howell, Tony; Lalloo, Fiona ; Newman, William; Smith, Miriam J.

In: Journal of Medical Genetics, 31.10.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

Evans, DG, Van Veen, E, Byers, H, Evans, S, Burghel, G, Woodward, E, Harkness, E, Eccles, DM, Greville-Heygate, S, Ellingford, J, Bowers, NL, Pereira, M, Wallace, AJ, Howell, S, Howell, T, Lalloo, F, Newman, W & Smith, MJ 2020, 'High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer', Journal of Medical Genetics.

APA

Evans, D. G., Van Veen, E., Byers, H., Evans, S., Burghel, G., Woodward, E., Harkness, E., Eccles, D. M., Greville-Heygate, S., Ellingford, J., Bowers, N. L., Pereira, M., Wallace, A. J., Howell, S., Howell, T., Lalloo, F., Newman, W., & Smith, M. J. (Accepted/In press). High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer. Journal of Medical Genetics.

Vancouver

Author

Evans, D Gareth ; Van Veen, Elke ; Byers, Helen ; Evans, Sarah ; Burghel, George ; Woodward, Emma ; Harkness, Elaine ; Eccles, Diana M ; Greville-Heygate, Stephanie ; Ellingford, Jamie ; Bowers, Naomi L ; Pereira, Marta ; Wallace, Andrew J ; Howell, Sacha ; Howell, Tony ; Lalloo, Fiona ; Newman, William ; Smith, Miriam J. / High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer. In: Journal of Medical Genetics. 2020.

Bibtex

@article{3b4f01c22acb4d4da2ebc60fe76a5029,
title = "High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer",
abstract = "Background:Whilst 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 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 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.",
author = "Evans, {D Gareth} and {Van Veen}, Elke and Helen Byers and Sarah Evans and George Burghel and Emma Woodward and Elaine Harkness and Eccles, {Diana M} and Stephanie Greville-Heygate and Jamie Ellingford and Bowers, {Naomi L} and Marta Pereira and Wallace, {Andrew J} and Sacha Howell and Tony Howell and Fiona Lalloo and William Newman and Smith, {Miriam J}",
year = "2020",
month = oct,
day = "31",
language = "English",
journal = "Journal of Medical Genetics",
issn = "1468-6244",
publisher = "BMJ ",

}

RIS

TY - JOUR

T1 - High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer

AU - Evans, D Gareth

AU - Van Veen, Elke

AU - Byers, Helen

AU - Evans, Sarah

AU - Burghel, George

AU - Woodward, Emma

AU - Harkness, Elaine

AU - Eccles, Diana M

AU - Greville-Heygate, Stephanie

AU - Ellingford, Jamie

AU - Bowers, Naomi L

AU - Pereira, Marta

AU - Wallace, Andrew J

AU - Howell, Sacha

AU - Howell, Tony

AU - Lalloo, Fiona

AU - Newman, William

AU - Smith, Miriam J

PY - 2020/10/31

Y1 - 2020/10/31

N2 - Background:Whilst 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 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 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.

AB - Background:Whilst 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 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 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.

M3 - Article

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 1468-6244

ER -