Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing

Shimelis H, Laduca H, Hu C, Hart SN, Na J, Thomas A, Akinhanmi M, Moore RM, Brauch H, Cox A, Eccles DM, Ewart-Toland A, Fasching P, Fostira F, Garber J, Godwin AK, Konstantopoulou I, Nevanlinna H, Sharma P, Yannoukakos D, Yao S, Feng BJ, Davis BT, Lilyquist J, Pesaran T, Goldgar DE, Polley EC, Dolinsky JS, Couch FJ (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Journal of the National Cancer Institute Oxford University Press

Book Volume: 110

Pages Range: 855-862

Journal Issue: 8

DOI: 10.1093/jnci/djy106

Abstract

BACKGROUND: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC. METHODS: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium (TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls. RESULTS: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants. CONCLUSIONS: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

Mayo Clinic US United States (USA) (US) Ambry Genetics US United States (USA) (US) Robert-Bosch-Krankenhaus DE Germany (DE) University of Sheffield GB United Kingdom (GB) University of Southampton GB United Kingdom (GB) Ohio State University US United States (USA) (US) National Centre for Scientific Research (NCSR) "Demokritos" GR Greece (GR) Dana–Farber Cancer Institute US United States (USA) (US) University of Kansas (KU) US United States (USA) (US) Helsingin yliopisto / University of Helsinki FI Finland (FI) Roswell Park Cancer Institute US United States (USA) (US) University of Utah US United States (USA) (US)

How to cite

APA:

Shimelis, H., Laduca, H., Hu, C., Hart, S.N., Na, J., Thomas, A.,... Couch, F.J. (2018). Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing. Journal of the National Cancer Institute, 110(8), 855-862. https://doi.org/10.1093/jnci/djy106

MLA:

Shimelis, Hermela, et al. "Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing." Journal of the National Cancer Institute 110.8 (2018): 855-862.

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