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Study: Study identifies genes associated with risk of triple-negative breast cancer

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This study is about:

The identification of genes that increase risk of .

Why is this study important?

National guidelines currently recommend and testing for women diagnosed with () at age 60 or younger or those who meet criteria based on a personal or family history of cancer. However, there are no guidelines for  genetic testing for other genes in patients. This study suggests that other non-BRCA genes also contribute to risk of .

Study findings: 

Panel testing in 10,901 patients revealed:

  • Inherited mutations were detected in approximately 14.5% of all participants.
    • Of these, approximately 9% of participants had mutations that were not in or .
  • Inherited mutations in the , , , , and genes were associated with a high risk of .
  • Inherited mutations in , , and were associated with moderate risk of .

What does this mean for me?

Genetic testing can help people with breast cancer learn if their cancer was caused by an . Panel testing, which tests for inherited mutations in many genes versus gene by gene testing, can identify those at increased risk for . Knowing that you are at increased risk for may impact your risk management strategies. Panel testing can also identify those patients who would benefit from targeted treatments such as patients with .

It is important to remember that this study only applied to risk and that some of the genes studied here could be associated with greater or different overall breast cancer risk or risk of other cancers such as ovarian or pancreatic cancer.

Results of this study suggest that all individuals with should undergo panel testing. If you have been diagnosed with , ask your health care providers if panel testing is right for you.

Posted 8/23/18

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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 PA, Fostira F, Garber J, Godwin AK, Konstantopoulou I, Nevanlinna H, Sharma P, Yannoukakos D, Yao S, Feng BJ, Tippin Davis B, Lilyquist J, Pesaran T, Goldgar DE, Polley EC, Dolinsky JS, Couch FJ.. " Risk Genes Identified by Multigene Panel Testing." J Natl Cancer Inst. 2018. 110: 855–862.


FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

This article is relevant for:

People diagnosed with triple-negative breast cancer

This article is also relevant for:

people with breast cancer

people with metastatic or advanced cancer

people with a genetic mutation linked to cancer risk


people with triple negative breast cancer

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Study background:

() is aggressive. These cancers lack , progesterone, and human epidermal growth factor () receptors, making them particularly difficult to treat given current treatment options. 
TNBC accounts for about 35% of breast cancer in African Americans and about 15% in whites.  At diagnosis, it is usually more advanced and is associated with an increased risk of recurrence and worse 5-year survival rates than other types of breast cancers.

Currently, NCCN guidelines recommend testing for patients diagnosed age 60 or younger. However, there are no recommendations for testing for other known breast cancer genes, because the risk of associated with other genes is unknown.

Researchers of this study wanted to better understand gene-specific risks for . Knowing who is at risk for should result in better clinical management for those at increased risk.

Researchers of this study wanted to know:

Of the genes known to increase breast cancer risk, which are associated with increased risk of ?

Study design:

Researchers used panel testing to identify genes associated with increased risk of .

  • Between March 2012 and June 2016, 10,901 patients with were tested using panel testing.
    • A clinical cohort of 8,753 patients was tested for 21 genes by Ambry, a clinical testing laboratory.
    • A Consortium cohort of 2,148 was tested for 17 genes by a Consortium of researchers.

Study findings: 

Panel test results in the clinical cohort revealed:

  • 14.4% of participants had pathogenic mutations in the one of the 21 genes tested.
    • 8.4% of patients had pathogenic mutations in or
    • 6% in non-BRCA genes.

Panel test results in the Consortium cohort revealed:

  • 14.5% of participants had pathogenic mutations in one of 17 genes tested.
    • 10.4% of participants had pathogenic mutations in or .
    • 4 % in non-BRCA genes.
  • (1.0%-1.6%) and (0.5%-0.7%) were the most common mutated non-BRCA genes.

Compared to controls, mutations were associated with high risk of (this finding supports previous studies).  Similarly, was associated with high risk of in both cohorts.  In the clinical cohort, mutations in , , and were also associated with high risk of .

In this study, and mutations were associated with an 18% and 10% lifetime risk of , respectively, followed by mutations in the (7%), (6%), and (5%) genes.

Moderate-risk risk genes were and , which were previously only associated with increased risk of ovarian cancer. Mutations in the gene, were also associated with modest risk of , consistent with the twofold increase in overall breast cancer risk shown in a recent study (the topic of a recent XRAYS review).

Mutations in , , , and were not associated with increased risk of .


While this study identifies genes associated with an increased risk of , more research will need to be done to refine the actual risk associated with each gene. The control data used in this study came from publicly available sequencing databases. Patients were not matched to controls (i.e. age, race, etc.).  However, these large sequencing databases likely provide reasonable population mutation frequencies and have been used successfully in other similar studies. 


Panel testing can identify women who are at increased risk of .  Mutations in BRCA1/2, , PAB2, and are associated with high risk of .  Women with mutations in these genes may benefit from increased screening and cancer prevention strategies. Patients with may also benefit from panel testing when considering targeted therapies such as pembrolizumab (Keytruda) for .

Posted 8/23/18

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network has guidelines on who should undergo genetic counseling and testing. If you have been diagnosed with breast cancer, you should speak with a genetics expert about genetic testing if any of the following apply to you:     

  • You have a blood relative who has tested positive for an  
  • You have any of the following:  
    • Breast cancer at age 50 or younger  
    • Male breast cancer at any age
    • Ovarian cancer at any age  
    • at any age 
    • Two separate breast cancer diagnoses
    • Eastern European Jewish ancestry and breast cancer at any age 
    • Lobular breast cancer and a family history of diffuse gastric cancer
    • For treatment decisions for people with breast cancer or people with early , breast cancer who are at high-risk for recurrence 
    • Testing of your tumor shows a mutation in a gene that is associated with


  • You have one or more close family members who have had:  
    • Young-onset or rare cancers 
    • Breast cancer at age 50 or younger
    • Male breast cancer, ovarian cancer, pancreatic cancer, or   cancer at any age
    • Two separate cancer diagnoses 
    • prostate cancer or  cancer that is high-risk or very-high-risk group. 

The American Society of Breast Cancer Surgeons (ASBrS) released guidelines in 2019 that recommend all women diagnosed with breast cancer have access to genetic testing for inherited mutations in breast cancer genes. 

If you are uncertain whether you meet the guidelines above and you are interested in or considering genetic testing, you should speak with a cancer genetics expert

Updated: 07/28/2023

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • Should I consider genetic testing?
  • Can you refer me to a genetics expert?
  • I had  testing which was negative. Should I consider panel testing?
  • Are there different risk management strategies that would benefit me?
  • Are there targeted treatments that are appropriate for me?

Open Clinical Trials
Open Clinical Trials

The following are studies enrolling people with , .  

A number of other clinical trials for patients with TNBC can be found here.

Updated: 02/22/2024

Open Clinical Trials
Open Clinical Trials

The following clinical trials include genetic counseling and testing. 

Other genetic counseling or testing studies may be found here.


Updated: 02/29/2024

Peer Support
Peer Support

The following organizations offer peer support services for people with, or at high risk for breast cancer:

Updated: 05/07/2024

Find Experts
Find Experts

The following resources can help you locate a genetics expert near you or via telehealth.

Finding genetics experts

  • The National Society of Genetic Counselors website has a search tool for finding a genetic counselor by specialty and location or via telehealth. 
  • InformedDNA is a network of board-certified genetic counselors providing this service by telephone. They can also help you find a qualified expert in your area for face-to-face genetic counseling if that is your preference. 
  • Gene-Screen is a third-party genetic counseling group that can help educate, support and order testing for patients and their families. 
  • JScreen is a national program from Emory University that provides low-cost at-home genetic counseling and testing with financial assistance available.
  • Grey Genetics provides access to genetic counselors who offer genetic counseling by telephone. 
  • The Genetic Support Foundation offers genetic counseling with board-certified genetic counselors. 

Related experts

Genetics clinics

Other ways to find experts

Updated: 07/21/2023

Who covered this study?

Science Daily

Triple-negative: Genes associated with risk for aggressive breast cancer This article rates 4.5 out of 5 stars

USA Today

Researchers identify genes linked to aggressive breast cancer This article rates 1.0 out of 5 stars

How we rated the media

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