BRCA Gene Testing for Breast and Ovarian Cancer Risk
When your personal or family history suggests you have inherited a BRCA mutation, such as you or someone in your family has had breast cancer before the age of 50 or ovarian cancer at any age, is a male with breast cancer, or when a BRCA1 or BRCA2 (BRCA1/2) mutation has been identified in a family member; a family history of certain types of pancreatic cancer or prostate cancer may also indicate a higher risk for BRCA1/2 mutation.
None, but genetic counseling is strongly recommended to confirm that you meet the testing criteria. If the sample collected will be saliva, it is recommended that you not eat, drink, or chew gum for at least an hour prior to your testing appointment. Also, kissing should also be avoided immediately prior to testing.
BRCA1 and BRCA2 are tumor suppressor genes. Normally, these genes help prevent cancer by producing proteins that suppress abnormal cell growth. Certain changes (mutations, pathogenic genetic variants) in these genes affect their normal function, thereby potentially allowing cells to grow unchecked. BRCA1/2 gene tests detect mutations in these genes that are linked mainly with hereditary breast and ovarian cancers (hereditary breast and ovarian cancer (HBOC) syndrome), although other types of cancer may be seen in HBOC families.
According to the American Cancer Society, more than 270,000 women are diagnosed with invasive breast cancer each year and over 21,000 with ovarian cancer.
- Of these cancers, about 3% of breast cancers and 10% of ovarian cancers are due to a mutation in BRCA1 or BRCA2 genes.
- Women with inherited BRCA1/2 mutations have a 70% lifetime risk of developing breast cancer.
- Breast cancer in women with inherited mutations is likely to develop at a younger age and more likely to develop in both breasts.
- Women with BRCA1/2 mutations have about a 15% to 70% lifetime risk of developing ovarian cancer.
Men with BRCA1/2 mutations are also at higher risk to develop breast cancer. The American Cancer Society states that about 2,600 men are diagnosed with invasive breast cancer annually.
- About 5% of breast cancers in men can be attributed to mutations in BRCA1/2.
- Men with a BRCA mutation have a 1% to 6% chance of developing breast cancer.
Men and women carrying BRCA1/2 mutations may be at slightly increased risk for other cancers, such as pancreatic cancer or prostate cancer, as well as fallopian tube cancer and peritoneal cancer. In the United States, BRCA1/2 mutations are more common in Jewish people of Ashkenazi (Eastern Europe) origin than in other racial and ethnic groups.
Each person has two copies of BRCA1 and BRCA2, one copy inherited from each parent. BRCA1/2 mutations are inherited and passed from generation to generation in an autosomal dominant inheritance pattern. This means that if a pathogenic variant is present in one copy of the gene, it can increase your risk of developing cancer.
How is the test used?
BRCA1 and BRCA2 tests are used to detect pathogenic genetic variants (mutations) that are known to increase the risk of breast and ovarian cancer. These genes are most often tested together. If a BRCA1 or BRCA2 mutation has been identified in a family member with breast and/or ovarian cancer, then that specific mutation can be tested in other family members to assess their risk. Specific BRCA1 and BRCA2 mutations are associated with some ethnic groups, such as those of Ashkenazi Jewish descent, and tests for just these specific pathogenic variants can be used to evaluate the risk of individuals in this group as a first-tier test.
Only about 1 in 400, or 0.25% of the U.S. population carries a BRCA1 or BRCA2 mutation, according to the National Breast Cancer Foundation. Because of this, genetic testing is not recommended for the general population.
When is it ordered?
Women from specific ancestries, or who have family or personal history of cancers associated with harmful mutations in the BRCA1/2 genes, are recommended to get risk assessments from primary care providers. Such risk assessments might involve, for example, talking to your healthcare practitioner about close relatives with breast or ovarian cancer (family history) and going through your medical history. If the assessment indicates you might be at high risk, the next step may be genetic counseling and possibly testing for pathogenic variants in the BRCA1/2 genes. Genetic counseling can help you fully understand the risks and benefits of testing and the implications of your results.
There are a variety of screening tools to help assess the risk of having a BRCA mutation and help determine whether you should consider testing. Some of the risk factors related to family history include:
- A relative with primary cancer in both breasts
- Relatives with breast cancer diagnosed before age 50 years
- A relative with both breast and ovarian cancer, or both breast and ovarian cancers in separate family members
- Multiple breast cancers in the family
- A single family member with two or more types of cancers related to BRCA1 or BRCA2 mutations
- Breast cancer in a male relative
- Ashkenazi Jewish ancestry
These factors should be considered for both your mother's and father's sides of the family.
You are also at a higher risk for a pathogenic mutation if you personally have had:
- Breast cancer that is "triple negative" (estrogen receptor (ER), progesterone receptor (PR), and HER2 negative)
- Breast cancer before age 50
- Male breast cancer
- Ovarian, fallopian tube or primary peritoneal (lining of the abdomen) cancer at any age
- Both breast and ovarian cancer
- Breast cancer more than once (multiple primary breast cancers)
What does the test result mean?
The presence of a pathogenic BRCA1 or BRCA2 mutation means that you have an increased risk for developing hereditary breast and/or ovarian cancer. It also indicates that your family members may be at increased risk for breast or ovarian cancer. However, even within a family with the same pathogenic BRCA1/2 mutation, not everyone will develop cancer. Family members who do develop cancer may get different types (breast versus ovarian) and may develop it at different times during their lives.
The degree of risk associated with a positive result is difficult to define for a specific person. Results must be interpreted along with your personal and family history. A genetic counselor can explain the meaning of your results, treatment options that are intended to decrease risk, and testing options for other family members.
According to the American Society of Clinical Oncology, estimates of lifetime risk for breast cancer in women with a BRCA1/2 genetic variant are 50% to 80%. Risk of ovarian cancer is 25% to 50% with BRCA1 genetic variant and 15% to 30% with BRCA2 genetic variant.
Up to 10% of women who undergo BRCA testing may receive a result indicating a genetic variant of uncertain significance (VUS). This occurs when a genetic test finds a BRCA1 or BRCA2 change that has not been previously identified or has an uncertain association with cancer risk. If this occurs, a genetic counselor can help you understand what this result may mean for your risk of developing cancer.
If my results are negative, does that mean I don't have increased risk of breast or ovarian cancer?
Genetic testing for pathogenic BRCA1 and BRCA2 gene mutations cannot detect 100% of these mutations. Thus, even with a negative result, there is very small chance that there is a pathogenic BRCA1/2 gene mutation present that was not identified by the testing. This is sometimes called your residual risk. In addition, there are other genes that may have pathogenic mutations that can contribute to a family's risk for breast cancer or other cancers. Genetic testing for just BRCA1/2 will only detect pathogenic mutations in these two genes. Therefore, if a mutation is present in another gene known to cause an increased risk for breast cancer, BRCA1 and BRCA2 gene testing will not detect it. If a pathogenic BRCA1/2 mutation has been found in your family because a relative has already had testing, and you then test negative for this variant, your residual risk is lower than if the variant in your family was not known. No test will take your risk to zero, but it may be described to you as similar to the risk in the general population.
In addition, sometimes a personal or family history of cancer may suggest a factor or combination of other factors that can contribute to risk. In these families, it is likely that common risk factors such as multiple shared genes that only sometimes cause cancer (low penetrance), shared environment and exposures, and shared lifestyle habits are increasing the risk for cancer above that of the general population. While members of these families typically do not have increased risks as high as those seen in individuals with pathogenic BRCA1/2 gene mutations, they often will have increased risks for cancer slightly above those of the general population and sometimes increased cancer surveillance is recommended.
Are people with BRCA mutations at risk for other cancers?
The BRCA gene's role in cancer risk is an active area of research. In addition to breast and ovarian cancer, the mutations have been linked to prostate and pancreatic cancer. A 2016 study published in the New England Journal of Medicine found BRCA1/2 gene variants in 11.8% of men with metastatic prostate cancer, compared with 2.7% of men without a cancer diagnosis. Citing this study, in 2019 the National Comprehensive Cancer Network updated its recommendations to include considering genetic testing for all men with high-risk, very high-risk, regional or metastatic prostate cancer, as well as those with a family history of prostate cancer or Ashkenazi Jewish ancestry. Experts also recommend that men carrying BRCA2 genetic variant begin prostate cancer screening at 40 years old.
Additionally, in both men and women, a BRCA genetic variant increases the risk of developing pancreatic cancer to 5%, compared with 1% for the average person. In 2020, the American Gastroenterological Association updated its guidelines to state that genetic testing and counseling should be considered for people who have family members with pancreatic cancer and that pancreatic cancer screening in high-risk individuals should begin at age 50.
If I have a positive result, should I tell my family members?
Positive test results (pathogenic or likely pathogenic variants identified) may have implications for other family members. When one member of a family is tested for pathogenic BRCA mutations, issues often arise about how to share this information with other family members. It may be helpful to seek advice from a genetic counselor about how to communicate results with other family members.
Should I have genetic counseling before or after I get tested?
Consultation with a genetic counselor about genetic testing both before and after you get tested cannot be overemphasized. There are many issues to be considered when preparing for a genetic test and upon learning the results, and a genetic counselor has the knowledge and expertise to help you sort through them.
If the BRCA mutation test is positive, what are my options for prevention or treatment?
If the BRCA mutation test is positive, the options include more frequent cancer screenings and screening starting earlier in life (e.g., mammography, breast MRI, blood tests for CA-125 or CA 15-3, or transvaginal ultrasonography), medications that could reduce risk (e.g., tamoxifen), or surgical removal of the ovaries or breasts. There are a number of variables involved and it is important to discuss your options with your healthcare provider and genetic counselor.
Where can I get this test?
The test can be ordered by a healthcare practitioner or genetic counselor. The sample will be sent to a laboratory that specializes in BRCA1/2 testing. The American Society of Clinical Oncology and the National Breast Cancer Coalition encourage women seeking the test to participate in long-term outcome studies to help gather information on the effectiveness of different check-up and treatment options. See the Related Content section of this article for links to additional information.
More recently, direct-to-consumer genetic testing has allowed people to test for gene variants such as BRCA without involving a healthcare provider or insurance company. Typically, you receive a test kit in the mail and then collect your own DNA sample by swabbing the inside of your cheek, then mail the sample back for analysis. Concerns about direct-to-consumer genetic testing include the potential for a high rate of error, especially in kits that have not been validated for clinical use, incomplete coverage of the BRCA genes (looking only at a handful of more common BRCA mutations), the risk of personal information being vulnerable, consumers being unaware of the importance of genetic counseling before and after testing, and out-of-pocket cost if insurance doesn't cover the testing kit. If you choose to use a direct-to-consumer genetic test, you should have the findings confirmed by a test done in an approved lab and discuss the findings and implications with a genetic counselor and your healthcare practitioner.
Besides breast and ovarian cancer risk assessment, is BRCA1/2 testing used for anything else?
Yes, BRCA1/2 testing may be used if a person already has cancer to see if they will respond to targeted therapy. In recent years, cancer drugs have been developed that target specific genetic changes (mutations) in tumors. Testing for the particular mutation that the drug targets can help predict who may benefit from the drug and who is not likely to respond. BRCA1/2 testing may be used to determine who will benefit from targeted drugs used to treat, for example, breast cancer, ovarian cancer, prostate cancer, or pancreatic cancer. A blood sample or a sample of your tumor may be requested for testing.
Is there anything else I should know?
BRCA1/2 testing is increasingly done as part of a larger panel of genes used to identify family hereditary cancer syndromes. Examples of other genes that may be included in the panel are CHEK2, PALB2, and ATM. The exact genes included in the panel will vary by testing laboratory. Your genetic counselor or healthcare practitioner can help you understand the importance of any additional genes included in panel testing.