BRCA Gene Mutation Testing

BRCA gene mutation testing shows whether you have inherited mutations, also called variants, in your BRCA1 or BRCA2 genes. It is performed using a blood sample, saliva, or cells removed from the inside of your cheek.

This test can reveal if you are at higher-than-average risk of developing certain cancers, especially breast or ovarian cancer. Knowing if a harmful mutation is present enables people to take steps to reduce their cancer risk.

Purpose of the test

Testing for BRCA genetic mutations reveals whether you have inherited gene mutations that can increase your risk of cancer. Mutations are permanent changes in the DNA that makes up a person’s genes.

Genes are passed to you from your parents and contain the information needed to build and maintain your body throughout your life. Genes affect traits that are passed down, like your hair color, how tall you are, and the likelihood you’ll develop particular diseases. Genetic mutations may contribute to the development of disease, although not everyone with a harmful genetic mutation will develop a particular disease.

All people have BRCA1 and BRCA2 genes, which enable your body to make proteins called tumor suppressors. When your BRCA genes are normal, the proteins they produce help keep your cells from developing abnormally.

If you inherited a harmful mutation in your BRCA1 or BRCA2 gene, your body is less efficient at making tumor suppressor proteins. This means it is easier for cells to grow abnormally and develop into cancer. The table below shows how BRCA gene mutations increase the lifetime risk of developing certain cancers:

Most of the time, these cancers are not caused by inherited gene mutations. Only about 5-10% of breast cancers and 15% of ovarian cancers are linked to mutations in the BRCA1 or BRCA2 genes. It is even less common for prostate or pancreatic cancer to be related to a gene mutation. But certain patterns in your personal or family medical history make it more likely that a harmful gene mutation may cause cancer.

What does BRCA gene mutation testing measure?

There are many different mutations in the BRCA1 and BRCA2 genes that may be detected during BRCA gene mutation testing. Which genes are tested depends on your circumstances:

• Most patients will have what is known as a multigene panel test. Multigene panel tests can detect a broad array of BRCA1 and BRCA2 mutations, as well as harmful mutations in other genes that can increase cancer risk.
• If a particular mutation has been found in a family member, you may be tested only for that known gene mutation.
• In Ashkenazi (Eastern European) Jews, three particular BRCA mutations are much more common than in other ethnic groups. These mutations are known as “founder mutations.” If testing is performed because of concerns about ancestry, testing may be limited to these three mutations.

When should I get BRCA genetic mutation testing?

Certain patterns of cancer in a family or in an individual raise suspicion that a harmful gene mutation is present. Expert groups, including the National Comprehensive Cancer Network and the American College of Medical Genetics recommend BRCA testing for people whose personal history includes:

• Female breast cancer diagnosed under the age of 45 to 50 or at any age if Ashkenazi Jewish
• Triple negative breast cancer (estrogen receptor (ER)-, progesterone receptor (PR)-, and HER2-negative) diagnosed at age 60 or younger
• Two or more primary breast cancers, with one diagnosed under the age of 50
• Breast cancer at any age and a relative with breast cancer under the age of 50
• Male breast cancer
• Ovarian, fallopian tube, or primary peritoneal cancer
• Metastatic prostate cancer
• High-grade prostate cancer and Ashkenazi Jewish heritage
• Pancreatic cancer

Testing may be recommended if your family history includes:

• A close relative (mother, father, sister, son, daughter, grandparent, grandchild, cousin, niece, nephew, aunt, uncle, or half-sibling) who meets one of the conditions above.
• A biological relative who has been found to have a harmful BRCA gene mutation.
• Ashkenazi Jewish adults, even if they have no personal or family risk of cancer.

Harmful mutations can be inherited from either your mother or your father, so the cancer history of both sides of your family should be considered.

Often, BRCA gene mutation testing is discussed after someone has been diagnosed with cancer. If a mutation is found in the cancer patient, other family members can be tested for that particular gene mutation. The patient’s parents, children, brothers, and sisters all have a 50% chance of having the same mutation.

How to get tested

If you are concerned that certain cancers run in your family, your first step may be talking to your primary care provider. Talk to your doctor about the types of cancers that have occurred in your family, how old people were when the cancer was found, if any relatives had more than one cancer, and if you have Ashkenazi Jewish ancestry. Based on this information, a doctor can assess the likelihood that you could have a genetic mutation in your family.

Your primary care provider can order BRCA gene testing for you or they may refer you to a genetic counselor. You can also find a genetics counselor on your own using the National Society of Genetic Counselors’ directory.

A genetic counselor can perform a risk assessment, weighing a number of factors to determine whether you are likely to have a harmful gene mutation. They can also discuss the pros and cons of genetic testing and answer any questions you may have. The counselor can order genetic testing for you and may be able to take a blood or saliva specimen for testing in their office. Or you may be asked to provide your sample at a lab.

Can I take the test at home?

The FDA has approved one direct-to-consumer test that detects some BRCA mutations. Direct-to-consumer tests do not require orders from a health care provider. In addition, there are other at-home tests which require physicians’ orders for you to be tested. The companies that sell these tests may contact your personal physician or provide a physician consultation on their website.

At-home tests may be appealing because they offer convenience and privacy. In addition, they are usually less expensive than tests ordered by a health care provider. However, they have some important drawbacks:

• At-home tests are limited in scope. For instance, the FDA-approved direct-to-consumer test detects only 3 out of the more than 1000 mutations known to occur in the BRCA1 and BRCA2 genes. This limitation means that, even if your test results are negative, you could still have one of the many BRCA mutations that weren’t tested for.
• If a harmful change is found, you will need to confirm the test in a clinically approved laboratory before you can proceed with steps to reduce your cancer risk.
• The support of an expert is important. A doctor or genetic counselor can help you understand the significance of your test results and advise you about reducing your cancer risk.

How much does the test cost?

The cost of BRCA gene mutation testing varies depending upon what lab is used, and how broad the test is. Some tests look only for a mutation known to run in your family. Others look for a much wider range of mutations. The cost of testing ranges from under $100 to over $2000.

If a doctor or genetic counselor orders genetic testing for you, your insurance usually covers the cost. Depending on your specific situation and health care plan, you may or may not be responsible for some out-of-pocket costs, such as copays and deductibles. If you do not have health insurance, you may still be able to get testing if your primary care provider or genetic counselor believes it is medically necessary. Many labs provide financial assistance for testing. It may also be possible to receive genetic counseling and undergo testing as part of a research study.

At-home genetic testing that includes BRCA1 and BRCA2 costs around $200 to $300. However, these tests typically only detect three BRCA mutations out of the more than 1000 which have been identified. If you have a positive result with an at-home test, you will need to confirm the result with a clinical laboratory.

Before the test

Usually, a blood sample will be taken by a health professional and sent to a specialty lab for analysis. Sometimes saliva or scrapings from the inside of your cheek may be used instead. To prepare for each type of test, take the following steps:

• Blood sample: no special preparation is needed. It is okay to eat and drink before the test.
• Saliva sample: be sure to follow guidelines from your doctor, nurse, or lab. You may be advised to avoid eating, drinking, or smoking for 30 minutes prior to the test. If you are using an in-home test kit, follow all instructions included with your kit.
• Cheek swab: you will be given directions for rinsing and washing your mouth before the test.

During the test

What to expect during a genetic test depends on the type of sample being collected:

• Blood sample: A health care provider will take a blood sample from a vein, usually in your arm. Blood draws typically take less than five minutes. First, the area will be cleaned with antiseptic, to kill any germs on your skin. Then an elastic band will be placed around your upper arm. Next, a needle attached to a tube will be stuck into your arm. You may feel a stinging sensation where the needle is inserted into your arm. After the blood is drawn into the sample tube, the elastic band is removed and the site where the blood was taken will be bandaged.
• Saliva sample: The provider will ask you to either spit into a tube, or will use a cotton ball or pad to absorb some saliva. It takes most people 2 to 5 minutes to fill a tube. A preservative will be used to ensure the sample is suitable for testing when received by the lab.
• Cheek swab: A health care provider will gently remove a sample of cells from the inside of your cheek with a small spatula-like instrument or foam brush. You may be given the instrument and instructed on how to do this yourself. This procedure is quick and painless.

After the test

After a blood draw, the site where the needle was inserted will be bandaged. Occasionally, people may have a little bruising at the site. You can drive and go about your normal activities after a blood test.

If a saliva sample or cells from inside your cheek were taken, no special precautions are needed afterward.

Receiving test results

It can take several weeks to receive your test results. Usually, the health care provider or genetic counselor who ordered your test will contact you to discuss your results. It is a good idea to schedule a visit to talk about how your results affect you and members of your family. Even if your test was ordered by your doctor, you may wish to follow up with a genetic counselor to discuss your results.

At-home genetic testing companies will report your results via a written report or a secure website. To learn how long it will take to get results, check the information that came with your test kit or the company’s website.

Interpreting BRCA gene mutation test results

Your test results will tell you whether a harmful mutation is present or absent. Sometimes, the test detects a mutation that is not well-understood. This is called a variant of uncertain significance:

• Negative results mean no known harmful mutations in your BRCA1 or BRCA2 genes were found. If a harmful variant is known to run in your family but was not detected in your sample, your result may be reported as a “true negative.” If no one in your family is known to have a harmful gene mutation, and your test is negative, it may be described as “uninformative.”
• Positive results mean a gene mutation that is known to be harmful was found. This may be described as pathogenic on your test report. Pathogenic means disease-causing. While having a pathogenic or harmful gene mutation does not necessarily mean you will develop a hereditary cancer, your risk is increased.
• Variants of uncertain significance (VUS) are variants in genes that have not previously been associated with a higher cancer risk. It is common for people who have multigene panel testing (which test many genes) to receive this result. Most VUS are later reclassified as negative. A small number may eventually be found to be harmful.

If your BRCA test shows a harmful gene mutation, talk to your doctor about how your test results will affect your medical care moving forward. If you already have cancer, having a BRCA mutation may affect your treatment.

If you have a harmful BRCA mutation and have not been diagnosed with cancer, a number of steps may be taken to reduce your risk. These include:

• Changes in cancer screening tests: Screening tests look for disease before symptoms are present. You may have earlier tests, more frequent tests, or different tests from the general population. These may include imaging tests, like mammograms and magnetic resonance imaging (MRI), and blood tests.
• Medication: Two drugs, tamoxifen and raloxifene, have been approved to prevent breast cancer in people at increased risk. If you are at risk of ovarian cancer, you may be encouraged to use birth control pills, which reduce the risk of this cancer by 50%.
• Surgery: If you are at increased risk of breast or ovarian cancer, surgery to remove breast tissue and your ovaries will reduce your risk. It’s important to discuss the risks and benefits of these surgeries with a doctor.

Are test results accurate?

Genetic testing is generally quite accurate. Although no test is right 100% of the time, the current methods used to detect genetic mutations produce trustworthy results. A false-positive result is very unlikely. A false positive result indicates an abnormality when none is actually present.

However, it is more likely that you could have a negative test result when you actually have a harmful gene mutation. This is because genetic tests will miss gene mutations they do not test for. Some genetic tests, such as direct-to-consumer tests, only look for particular gene mutations. They can miss other BRCA mutations or harmful mutations in other genes that may increase cancer risk.

In addition, our understanding of gene mutations and cancer risk is growing rapidly. Research is ongoing to discover new gene mutations that increase a person’s risk of cancer.

Do I need follow-up tests?

If you receive a positive test result on a direct-to-consumer test, it will need to be confirmed with a test at a clinically-approved laboratory.

If you are found to have a harmful mutation, cancer screening tests to detect cancer early may be ordered for you. A health care provider will advise you on what tests are most appropriate for you. Tests may include:

• Mammograms or magnetic resonance imaging (MRI) to check for breast cancer
• Ultrasound and CA-125 to check for ovarian cancer
• Prostate-specific antigen (PSA) test to check for prostate cancer
• Imaging tests like MRI or ultrasound to check for pancreatic cancer

Questions for your doctor about test results

It may be helpful to ask your doctor or genetic counselor these questions:

• What do my test results say about my cancer risk?
• Do you recommend taking preventive measures to reduce my cancer risk? What are the risks and benefits of those procedures?
• Do my family members also need to be tested?
• How will I know if a variant of uncertain significance (VUS) is reclassified as harmful or not harmful?
• How do these test results change my medical care moving forward?

More information about BRCA gene testing and inherited cancer risk is available in the following resources:

• National Cancer Institute: BRCA Gene Mutations: Cancer Risk and Genetic Testing
• CDC: Genetic Testing for Hereditary Breast and Ovarian Cancer
• American Society of Clinical Oncology: Hereditary Breast and Ovarian Cancer
• National Society of Genetic Counselors: Find a Genetic Counselor
• Facing Hereditary Cancer Risk Empowered: Genetic Testing for Inherited Mutations

Sources

A.D.A.M. Medical Encyclopedia. What you need to know about blood tests. Updated April 24, 2019. Accessed May 30, 2021. https://medlineplus.gov/ency/article/003414.htm

A.D.A.M. Medical Encyclopedia. Venipuncture. Updated April 26, 2019. Accessed May 26, 2021. https://medlineplus.gov/ency/article/003423.htm

A.D.A.M. Medical Encyclopedia. BRCA1 and BRCA2 gene testing. Updated July 20, 2019. Accessed May 26, 2021. https://medlineplus.gov/ency/patientinstructions/000690.htm

A.D.A.M. Medical Encyclopedia. Buccal smear. Updated May 25, 2021. Accessed May 26, 2021. https://medlineplus.gov/ency/article/003414.htm

American Cancer Society. Genetic counseling and testing for breast cancer risk. Updated September 10, 2019. Accessed May 26, 2021. https://www.cancer.org/cancer/breast-cancer/risk-and-prevention/genetic-testing.html

American Cancer Society. Key statistics for breast cancer in men. Updated January 12, 2021. Accessed May 30, 2021. https://www.cancer.org/cancer/breast-cancer-in-men/about/key-statistics.html

American Society of Clinical Oncology. How to share genetic test results with family. Updated March 30, 2017. Accessed May 30, 2021. https://www.cancer.net/blog/2017-03/how-share-genetic-test-results-with-family

American Society of Clinical Oncology. Hereditary breast and ovarian cancer. Updated November 2020. Accessed May 25, 2021. https://www.cancer.net/cancer-types/hereditary-breast-and-ovarian-cancer

American Society of Clinical Oncology. Genetic testing coverage and reimbursement. Date unknown. Accessed May 26, 2021. https://www.asco.org/practice-policy/cancer-care-initiatives/genetics-toolkit/genetic-testing-coverage-reimbursement

Centers for Disease Control and Prevention. How to collect a saliva (spit) sample for parents. Updated June 12, 2013. Accessed May 26, 2021. https://www.cdc.gov/ncbddd/birthdefects/documents/foa/draft_salivainstructionsparent_engtest.pdf

Centers for Disease Control and Prevention. Hereditary breast cancer. Updated April 5, 2019. Accessed May 26, 2021. https://www.cdc.gov/cancer/breast/young_women/bringyourbrave/hereditary_breast_cancer/index.htm

Centers for Disease Control and Prevention. Genetic testing for hereditary breast and ovarian cancer. Updated June 10, 2019. Accessed May 25, 2021. https://www.cdc.gov/genomics/disease/breast_ovarian_cancer/testing.htm

Centers for Disease Control and Prevention Genetic counseling. Updated March 23, 2020. Accessed May 25, 2021. https://www.cdc.gov/genomics/gtesting/genetic_counseling.htm

Centers for Disease Control and Prevention. Genetic counseling for hereditary breast and ovarian cancer. Updated March 25, 2020. Accessed May 26, 2021. https://www.cdc.gov/genomics/disease/breast_ovarian_cancer/counseling.htm

Centers for Medicare and Medicaid Services. Affordable care act implementation FAQs. Date Unknown. Accessed May 26, 2021. https://www.cms.gov/CCIIO/Resources/Fact-Sheets-and-FAQs/aca_implementation_faqs12

Food and Drug Administration. Direct-to-consumer tests. Updated December 20, 2019. Accessed May 30, 2021. https://www.fda.gov/medical-devices/in-vitro-diagnostics/direct-consumer-tests

Facing Hereditary Risk Empowered. BRCA counseling and testing for women, Updated 2021. Accessed May 26, 2021. https://www.facingourrisk.org/privacy-policy-legal/laws-protections/ACA/screening-preventive-services/genetic-counseling-testing

Healthcare.gov. Preventive care benefits for women. Date unknown. Accessed May 26, 2021. https://www.healthcare.gov/preventive-care-women/

Hofman LF. Human saliva as a diagnostic specimen. J Nutr. 2001 May;131(5):1621S-5S. doi: 10.1093/jn/131.5.1621S.

Hu C, Hart SN, Polley EC, Gnanaolivu R, Shimelis H, Lee KY, Lilyquist J, Na J, Moore R, Antwi SO, Bamlet WR, Chaffee KG, DiCarlo J, Wu Z, Samara R, Kasi PM, McWilliams RR, Petersen GM, Couch FJ. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA. 2018 Jun 19;319(23):2401-2409. doi: 10.1001/jama.2018.6228.

Isaacs C, Peshkin BN. Cancer risk and management of BRCA1/2 carriers without cancer. In: Chagpar AB, Goff B, Burstein HJ, eds. UpToDate. Updated April 21, 2021. Accessed May 26, 2021. https://www.uptodate.com/contents/cancer-risks-and-management-of-brca1-2-carriers-without-cancer

Makhnoon S, Shirts BH, Bowen DJ. Patients’ perspectives of variants of uncertain significance and strategies for uncertainty management. J Genet Couns. 2019 Apr;28(2):313-325. doi: 10.1002/jgc4.1075.

MedlinePlus: National Library of Medicine. Genetic testing. Updated June 20, 2014. Accessed June 1, 2021. https://medlineplus.gov/genetictesting.html

MedlinePlus: National Library of Medicine. BRCA genetic test. Updated July 23, 2018. Accessed May 30, 2021. https://medlineplus.gov/lab-tests/brca-test/

MedlinePlus: National Library of Medicine. What is the cost of genetic testing? Updated September 21, 2020. Accessed June 1, 2021. https://medlineplus.gov/genetics/understanding/testing/costresults/

MedlinePlus: National Library of Medicine. What are the benefits and risks of direct-to-consumer testing? Updated April 18, 2021. Accessed May 30, 2021. https://medlineplus.gov/genetics/understanding/dtcgenetictesting/dtcrisksbenefits/

MedlinePlus: National Library of Medicine. How to prepare for a lab test. Updated March 8, 2021. Accessed May 30, 2021. https://medlineplus.gov/lab-tests/how-to-prepare-for-a-lab-test/

National Cancer Institute. Breast cancer risk in American women. Updated December 16, 2020. Accessed May 30, 2021. https://www.cancer.gov/types/breast/risk-fact-sheet

National Cancer Institute. BRCA gene mutations, cancer risk and genetic testing. Updated November 19, 2020. Accessed May 25, 2021. https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

National Cancer Institute. Genetic testing fact sheet. Updated March 15, 2019. Accessed June 1, 2021. https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet

National Cancer Institute. Cancer stat facts: Ovarian cancer. Date unknown. Accessed May 30, 2021. https://seer.cancer.gov/statfacts/html/ovary.html

National Cancer Institute. Cancer stat facts: Pancreatic cancer. Date unknown. Accessed May 30, 2021. https://seer.cancer.gov/statfacts/html/pancreas.html

National Cancer Institute. Cancer stat facts: Prostate cancer. Date unknown. Accessed May 30, 2021. https://seer.cancer.gov/statfacts/html/prost.html

National Comprehensive Cancer Network. Genetic/familial high risk assessment: Breast, ovarian, and pancreatic. Updated November 20, 2020. Accessed May 27, 2021. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf

National Human Genome Research Institute. Human genome project FAQ. Updated February 24, 2020. Accessed May 25, 2021. https://www.genome.gov/human-genome-project/Completion-FAQ

Peshkin BN, Isaacs C. Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes. In: Changpar AB, Goff B, Burstein HJ, eds. UpToDate. Updated February 19, 2021. Accessed May 25, 2021. https://www.uptodate.com/contents/genetic-testing-and-management-of-individuals-at-risk-of-hereditary-breast-and-ovarian-cancer-syndromes

Peshkin BN, Isaacs C. Patient Education: Genetic testing for hereditary breast, ovarian, pancreatic, and prostate cancer. In: Hayes DF, Raby BA, eds. UpToDate. Updated December 1, 2020. Accessed May 25, 2021. https://www.uptodate.com/contents/genetic-testing-for-hereditary-breast-ovarian-prostate-and-pancreatic-cancer-beyond-the-basics

United States Preventive Services Task Force. Final recommendation statement: BRCA related cancer: Risk assessment, genetic counseling, and genetic testing. Published August 20, 2019. Accessed May 25, 2021. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing

U.S. Department of Health and Human Services. My Healthfinder: Talk with a doctor if breast or ovarian cancer runs in your family. Updated October 15, 2020. Accessed May 27, 2021. https://health.gov/myhealthfinder/topics/health-conditions/cancer/talk-doctor-if-breast-or-ovarian-cancer-runs-your-family