Breast cancer survivors
People with a genetic mutation linked to cancer risk
Triple negative breast cancer
Women under 45
Women over 45
Panel testing can identify women who are at increased risk for breast cancer. However, those at risk for triple-negative breast cancer cannot easily be identified because other than BRCA1, genes that increase the risk for triple-negative breast cancer are unknown. A new study uses panel testing to identify which genes increase the risk for triple-negative breast cancer. (8/23/18)
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The identification of genes that increase risk of triple-negative breast cancer.
National guidelines currently recommend BRCA1 and BRCA2 testing for women diagnosed with triple-negative breast cancer (TNBC) 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 TNBC patients. This study suggests that other non-BRCA genes also contribute to risk of TNBC.
Panel testing in 10,901 triple-negative breast cancer patients revealed:
Genetic testing can help people with breast cancer learn if their cancer was caused by an inherited mutation. Panel testing, which tests for inherited mutations in many genes versus gene by gene testing, can identify those at increased risk for TNBC. Knowing that you are at increased risk for TNBC may impact your risk management strategies. Panel testing can also identify those TNBC patients who would benefit from targeted treatments such as patients with Lynch syndrome.
It is important to remember that this study only applied to TNBC 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 TNBC should undergo panel testing. If you have been diagnosed with TNBC, consider asking your health care providers if panel testing is right for you.
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The National Comprehensive Cancer Network (NCCN) guidelines currently recommend BRCA1 and BRCA2 testing for women diagnosed with triple-negative breast cancer (TNBC) at age 60 or younger or those who meet criteria based on a personal or family history of cancer.
Triple-negative breast cancer (TNBC) is aggressive. These cancers lack estrogen, progesterone, and human epidermal growth factor (HER2) 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 BRCA testing for TNBC patients diagnosed age 60 or younger. However, there are no recommendations for testing for other known breast cancer genes, because the risk of TNBC associated with other genes is unknown.
Researchers of this study wanted to better understand gene-specific risks for TNBC. Knowing who is at risk for TNBC should result in better clinical management for those at increased risk.
Of the genes known to increase breast cancer risk, which are associated with increased risk of TNBC?
Researchers used panel testing to identify genes associated with increased risk of TNBC.
Panel test results in the clinical cohort revealed:
Panel test results in the TNBC Consortium cohort revealed:
Compared to controls, BRCA1 mutations were associated with high risk of TNBC (this finding supports previous studies). Similarly, BRCA2 was associated with high risk of TNBC in both cohorts. In the clinical cohort, mutations in PALB2, BARD1, and RAD51D were also associated with high risk of TNBC.
In this study, BRCA1 and PALB2 mutations were associated with an 18% and 10% lifetime risk of TNBC, respectively, followed by mutations in the BARD1 (7%), BRCA2 (6%), and RAD51D (5%) genes.
Moderate-risk TNBC risk genes were BRIP1 and RAD51C, which were previously only associated with increased risk of ovarian cancer. Mutations in the Lynch syndrome gene, MSH6 were also associated with modest risk of TNBC, consistent with the twofold increase in overall breast cancer risk shown in a recent study (the topic of a recent XRAYS review).
Mutations in ATM, CHEK2, NBN, and RAD50 were not associated with increased risk of TNBC.
While this study identifies genes associated with an increased risk of TNBC, 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 DNA 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 TNBC. Mutations in BRCA1/2, BARD1, PAB2, and RAD51D are associated with high risk of TNBC. Women with mutations in these genes may benefit from increased screening and cancer prevention strategies. Patients with TNBC may also benefit from panel testing when considering targeted therapies such as pembrolizumab (Keytruda) for Lynch syndrome.
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