Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Aug 1;110(8):855-862.
doi: 10.1093/jnci/djy106.

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

Hermela Shimelis  1 , Holly LaDuca  2 , Chunling Hu  1 , Steven N Hart  3 , Jie Na  3 , Abigail Thomas  3 , Margaret Akinhanmi  1 , Raymond M Moore  3 , Hiltrud Brauch  4   5   6 , Angela Cox  7 , Diana M Eccles  8 , Amanda Ewart-Toland  9 , Peter A Fasching  10   11   12 , Florentia Fostira  13 , Judy Garber  14 , Andrew K Godwin  15 , Irene Konstantopoulou  13 , Heli Nevanlinna  16 , Priyanka Sharma  15 , Drakoulis Yannoukakos  13 , Song Yao  17 , Bing-Jian Feng  18 , Brigette Tippin Davis  2 , Jenna Lilyquist  3 , Tina Pesaran  2 , David E Goldgar  18 , Eric C Polley  3 , Jill S Dolinsky  2 , Fergus J Couch  1   3
Affiliations

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

Hermela Shimelis et al. J Natl Cancer Inst. .

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Absolute risk estimates to age 85 for overall breast cancer and triple-negative breast cancer. A) Age-related risk curves for overall breast cancer for six genes are shown as colored lines. B) Age-related risk curves for TNBC for six genes are shown as colored dashed lines. TNBC = triple-negative breast cancer.
See this image and copyright information in PMC

References

    1. Boyle P. Triple-negative breast cancer: Epidemiological considerations and recommendations. Ann Oncol. 2012;23(suppl 6):vi7–v12. - PubMed
    1. Plasilova ML, Hayse B, Killelea BK, et al. Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database. Medicine (Baltimore). 2016;9535:e4614. - PMC - PubMed
    1. Li X, Yang J, Peng L, et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. 2017;1612:279–287. - PubMed
    1. Couch FJ, Hart SN, Sharma P, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. 2015;334:304–311. - PMC - PubMed
    1. Buys SS, Sandbach JF, Gammon A, et al. A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer. 2017;12310:1721–1730. - PubMed

Publication types

MeSH terms

Substances