Last Updated on March 17, 2025
BRCA gene mutations are mutations that occur in BRCA genes. These are linked to increased risk of breast and other cancers.
Read more about Breast Cancer: Risk Factors, classification, Diagnosis, and Treatment
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What are BRCA Genes?
BRCA stands for “BReast CAncer gene”.
There are two types of BRCA genes – BRCA1 and BRCA2. Every human being has both these BRCA genes in their body.
Despite their name, BRCA genes do not cause breast cancer.
On the contrary, these genes play a major role in preventing breast cancer.
These genes produce tumor suppressor proteins which help in repairing damaged DNA and thus prevent the uncontrolled growth of cells that can lead to cancer. Because of this, the BRCA genes are known as tumor suppressor genes.
BRCA Gene Mutations
In some people, these tumor suppressor genes may become altered or broken. This is called gene mutation. Gene mutation results in improper functioning of the genes.
As a result of a mutation in BRCA genes, damage to DNA (which occurs normally) does not get repaired properly. This causes the cells to develop genetic alterations leading to their growth and division rapidly in an uncontrolled way ultimately leading to cancer.
A mutated BRCA gene thus can’t repair broken DNA and prevent cancer formation.
People with a BRCA gene mutation are more likely to develop breast cancer, ovarian cancer, etc. Also, they are more likely to develop cancer at a younger age.
People carrying these mutated genes can also pass the defective genes down to his or her offspring.
BRCA1 or BRCA2 mutation can be inherited from either mother or father. If one of the parents carries a mutation, there is a 50% chance that the offsprings would inherit the mutation.
The harmful effects of mutations in BRCA1 and BRCA2 genes exist even when a person’s second copy of the gene is normal (the one inherited from the normal parent).
Prevalence of BRCA Mutations
The prevalence of BRCA1 and BRCA2 mutations is rare in the general population. Prevalence is different for different ethnic groups.
In the U.S., about 1 in 400 people carry these gene mutations. Ashkenazi Jewish population shows a much higher prevalence with about 1 in 40 people carrying a BRCA1 or BRCA2 mutation. It is estimated that approximately 1 million people in the United States carry a BRCA gene mutation.
However, less than 10 % are aware of the fact that they have a mutation that increases their risk of developing cancer.
Effects of BRCA Gene Mutations
The risk of developing certain cancers is greatly increased if a person inherits the mutated BRCA1 or BRCA2 genes. The most important of these is Hereditary Breast and Ovarian Cancer Syndrome (HBOC).
Breast cancer
BRCA gene mutations account for about 5% to 10% of all breast cancers in females. About 72% of women having BRCA1 gene mutation and 69% of women having BRCA2 gene mutations are likely to develop breast cancer in their lifetime. In contrast, less than 12% of women in the general population are likely to develop breast cancer in their lifetime.
BRCA1 and 2 mutations explain a large portion of hereditary breast cancers.
Women with hereditary breast cancer due to BRCA mutations are at an increased risk of developing recurrent breast cancer.
Breast cancers associated with BRCA mutation are also more likely to be triple negative breast cancer, which is usually more aggressive and difficult to treat.
Read more about Triple Negative Breast Cancer
Ovarian cancer
BRCA gene mutations also increase the risk of ovarian cancer. About 44% of women with BRCA1 gene mutation and about 17% of women with a BRCA2 mutation are likely to develop ovarian cancer. On the other hand, only about 1.3% of women in the general population are going to have ovarian cancer.
Male breast cancer
The presence of BRCA 1 and 2 mutations are also responsible for a significant number of male cancers. The lifetime risk with BRCA2 mutations is slightly more than with BRCA1 mutations.
Read more about Male Breast Cancer
Besides these, mutations in BRCA1 and BRCA2 increase the risk of several other cancers in both men and women. These include:
- Peritoneal cancer
- Pancreatic cancer
- Cancer of the fallopian tube in females
- Prostate cancer in men
How to Test for BRCA1 and BRCA2 Gene Mutations (BRCA Gene Testing)?
BRCA gene mutations can be detected by genetic tests.
The sample required for these tests is either a blood or saliva sample.
DNA material extracted from these samples is subjected to genetic testing to find out if BRCA1 or BRCA2 gene mutations are present. It takes about a few weeks to a month to get the test results.
Besides BRCA1 and BRCA2 genes, mutations in other genes have been identified that increase the risk of breast and ovarian cancer. These include mutations in the genes PALB2, TP53, CDH1, and CHEK2, which increase the risk of breast cancer, and in RAD51C, RAD51D, and STK11, which increase the risk of ovarian cancer.
Genetic testing for all these mutations can be carried out as part of Multigene (panel) testing.
Who All Should Undergo BRCA Gene Testing?
BRCA gene mutations are rare in the general population. Hence BRCA testing should only be done in those persons whose personal or family history suggests the possible presence of these harmful mutations.
BRCA1 and BRCA2 related hereditary breast and ovarian cancer is suspected in persons who have a personal or family history of these cancers. Family history is said to be present when 1st, 2nd, or 3rd-degree relative from either the maternal or paternal side is affected by these cancers.
- A personal history of breast or ovarian cancer
- diagnosed at a young age
- breast cancer affecting both the breasts
- presence of both ovarian and breast cancer
- A family history of breast, ovarian, fallopian tube, peritoneal, prostate, or pancreatic cancer.
- A male relative having breast cancer.
- A relative with a known mutation in BRCA1 or BRCA2 genes.
- A young family member (< 50 years ) having breast cancer in both the breasts
- Two or more relatives with ovarian cancer
- A person having triple negative breast cancer with or without a family history
- A person having Ashkenazi Jewish ethnicity.
BRCA gene testing is not recommended for children less than 18 years of age, even if they have a strong family history. This is because even if tested positive, there are no strategies that can reduce the risk in children and moreover children’s risks of developing cancer associated with BRCA gene mutation is extremely low.
Uses of BRCA Gene Testing
- To assess the risk of hereditary breast, ovarian and other cancers.
- For early detection of hereditary cancers leading to better survival rates.
- To decide the best treatment options for a patient
Interpretation of the BRCA Gene Test Result
Positive result
A positive test result means that a person has a mutation in one of the breast cancer genes, BRCA1 or BRCA2, and therefore is at an increased risk of developing certain cancers (most commonly breast or ovarian cancer).
However, a positive result doesn’t mean that an individual will definitely develop cancer.
If tested positive, a person may take specific measures including:
- Increased frequency of cancer screening.
- Dietary and lifestyle changes to reduce the risk of cancer.
- Medications or procedures to reduce cancer risk.
Follow up treatment and care depends on several factors. These include age, medical history, previous treatments including surgeries and personal choices.
A positive test result in a person also has important implications for other family members. A person who inherits a BRCA1 or BRCA2 gene mutation can pass the mutation to his or her own children. There is a 50% chance of passing down the harmful mutated gene to the offspring.
Negative result
A negative test result means that BRCA gene mutations were not found. It does not mean that a person can never develop breast or ovarian or other cancers.
If a tested person’s close relative is known to carry a BRCA1 or BRCA2 gene mutation, a negative test result means that the person does not carry that particular mutation and will not pass it on to his or her children. Such a test result is called a true negative. The risk of developing cancer in such a person is similar to that of the general population.
In some cases, the tested person may have a family history that suggests the likelihood of having a BRCA gene mutation. However, no such mutation is found even after complete gene testing in the person as well as other family members. In such cases, the significance of a negative test result is less clear.
- Although the BRCA gene test can detect the majority of BRCA mutations, it is possible that the person was carrying a mutation that the test was not able to detect.
- Also, the person may be carrying a mutation that has not previously been identified by scientists.
- Finally, the person and family members may be carrying another hereditary cancer gene mutation that will be negative with BRCA gene testing.
Hence it is important to consult a genetic counselor who can guide the person regarding the significance of test results.
Ambiguous or uncertain result
Sometimes a genetic test finds a mutation in BRCA genes that have not been previously associated with cancer. In such cases, it is uncertain whether the specific genetic alteration is harmful or not. About 10% of individuals undergoing the test may get ambiguous results.
Genetic counseling can help a person to understand the significance of such a result and to decide proper follow-up.
More research and studies related to BRCA gene changes may in the future help to classify these uncertain results as either harmful or not.
What if the BRCA Gene Test is Positive?
It’s natural to feel anxious if a person tests positive for the BRCA1 or BRCA2 test.
Although these gene mutations are known to markedly increase the risk of developing certain cancers, many people who carry these mutations will never develop cancer.
Even if they have cancer, early diagnosis and treatment result in a better outcome and improved survival rates.
Screening
Persons who test positive for BRCA gene testing should undergo screening for breast cancer more frequently. Also, they can start the screening tests at a younger age ( 25 years of age) as compared to the general population. Screening tests for breast cancer include breast self-examinations, clinical examinations, mammograms, MRIs, etc.
Read more about Screening of Breast Cancer
Read more about MRI in Breast Cancer- Indications and Procedure
Early detection of breast cancer, when it is still localized, leads to a better outcome. The survival rate of early-stage breast cancer is more than 98%.
Read more about Staging of Breast Cancer
For ovarian cancer, there are no effective screening methods although clinical examinations, transvaginal ultrasound, and a blood test for measuring CA-125 may be carried out.
Preventive Surgery
Women who test positive for BRCA gene mutations can choose to undergo preventative surgery so as to reduce the risk of developing breast cancer.
A preventative double mastectomy (prophylactic bilateral mastectomy) is the surgical procedure wherein both the breasts are removed even before cancer has developed in the breasts. Mastectomy may be followed by breast reconstruction surgery for cosmetic reasons.
Some women may also opt for surgical removal of both sided fallopian tubes and ovaries (prophylactic bilateral salpingo-oophorectomy). Removal of ovaries also reduces estrogen levels in the body; thereby protecting against breast cancer.
Such type of surgery can reduce the risk of developing breast cancer by about 90%. However, the risk can’t be eliminated entirely. Moreover, any surgery itself carries a certain amount of risk. Women must consider all the pros and cons of such an extreme surgical procedure before taking a final decision.
Chemoprevention
Medicines may be given to reduce the risk of cancer. Two drugs (tamoxifen and raloxifene) have been approved by the U.S. Food and Drug Administration to reduce the risk of breast cancer in women who are at increased risk. However, they have not been specifically recommended for women with BRCA1 or BRCA2 mutations. Still, they could be used for prevention by women who don’t want to or cannot undergo surgery.
The use of oral contraceptives are known to reduce the risk of ovarian cancer by about 50%. This risk reduction applies to women in the general population as well as those carrying BRCA1 or BRCA2 gene mutations.
Emotional counseling
It forms an important part of BRCA gene testing since the test results may be associated with fear, anxiety and/or feeling of guilt.
Treatment of BRCA Gene Associated Breast Cancer
Treatment of breast cancers associated with BRCA1 and BRCA2 mutations is similar to breast cancers not related to BRCA mutations.
However, some drug therapies may be more or less effective in treating BRCA1 or 2 related breast cancers than other breast cancers. Since many BRCA breast cancers are triple negative, this implies that hormonal therapy is not effective in treating BRCA associated breast cancer. This includes drugs like tamoxifen, aromatase inhibitors, Herceptin (trastuzumab), etc.
PARP inhibitors olaparib (Lynparza) and talazoparib (Talzenna) are used to treat some BRCA1 or 2 related metastatic breast cancers.
Read more about Metastasis or Metastatic Disease
Platinum-based chemotherapy drugs (such as carboplatin) may be better at treating BRCA related breast cancers than other breast cancers.
Outlook of BRCA Gene Mutation Related Breast Cancer
The outcome and chances of survival of BRCA1 or BRCA2 mutations related breast cancer are similar to that of breast cancer patients without BRCA1 or BRCA2 mutations.
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