@article{b01c79eeb1c14062b6ab87207c59ea34,
title = "Penetrance of Breast Cancer Susceptibility Genes from the eMERGE III Network",
abstract = "Background: Unbiased estimates of penetrance are challenging but critically important to make informed choices about strategies for risk management through increased surveillance and risk-reducing interventions. Methods: We studied the penetrance and clinical outcomes of 7 breast cancer susceptibility genes (BRCA1, BRCA2, TP53, CHEK2, ATM, PALB2, and PTEN) in almost 13 458 participants unselected for personal or family history of breast cancer. We identified 242 female participants with pathogenic or likely pathogenic variants in 1 of the 7 genes for penetrance analyses, and 147 women did not previously know their genetic results. Results: Out of the 147 women, 32 women were diagnosed with breast cancer at an average age of 52.8 years. Estimated penetrance by age 60 years ranged from 17.8% to 43.8%, depending on the gene. In clinical-impact analysis, 42.3% (95% confidence interval = 31.3% to 53.3%) of women had taken actions related to their genetic results, and 2 new breast cancer cases were identified within the first 12 months after genetic results disclosure. Conclusions: Our study provides population-based penetrance estimates for the understudied genes CHEK2, ATM, and PALB2 and highlights the importance of using unselected populations for penetrance studies. It also demonstrates the potential clinical impact of genetic testing to improve health care through early diagnosis and preventative screening.",
author = "Xiao Fan and Julia Wynn and Ning Shang and Cong Liu and Alexander Fedotov and Hallquist, {Miranda L.G.} and Buchanan, {Adam H.} and Williams, {Marc S.} and Smith, {Maureen E.} and Christin Hoell and Rasmussen-Torvik, {Laura J.} and Peterson, {Josh F.} and Wiesner, {Georgia L.} and Murad, {Andrea M.} and Jarvik, {Gail P.} and Gordon, {Adam S.} and Rosenthal, {Elisabeth A.} and Stanaway, {Ian B.} and Crosslin, {David R.} and Larson, {Eric B.} and Leppig, {Kathleen A.} and Henrikson, {Nora B.} and Williams, {Janet L.} and Rongling Li and Scott Hebbring and Chunhua Weng and Yufeng Shen and Crew, {Katherine D.} and Chung, {Wendy K.}",
note = "Funding Information: This work was supported by the NHGRI through the following grants: U01HG8657 (Group Health Cooperative/University of Washington); U01HG8685 (Brigham and Women{\textquoteright}s Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children{\textquoteright}s Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children{\textquoteright}s Hospital of Philadelphia); U01HG8673 (Northwestern University); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare/Broad Institute); and U01HG8664 (Baylor College of Medicine). Funding Information: This work was supported by the NHGRI through the following grants: U01HG8657 (Group Health Cooperative/ University of Washington); U01HG8685 (Brigham and Women's Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children's Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children's Hospital of Philadelphia); U01HG8673 (Northwestern University); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare/ Broad Institute); and U01HG8664 (Baylor College of Medicine). Publisher Copyright: {\textcopyright} 2021 Oxford University Press. All rights reserved.",
year = "2021",
month = aug,
day = "1",
doi = "10.1093/jncics/pkab044",
language = "English (US)",
volume = "5",
journal = "JNCI Cancer Spectrum",
issn = "2515-5091",
publisher = "Oxford University Press",
number = "4",
}
