A Gift From Birth

About Brca genes

Inherited BRCA mutations are associated with breast cancer, ovarian cancer, and some other cancers.²⁶ Clinical studies showed that:

About 72% of women who inherit a harmful BRCA1 mutation will develop breast cancer by the age of 80.²⁶

About 69% of women who inherit a harmful BRCA2 mutation will develop breast cancer by the age of 80.²⁶

People inherited with harmful BRCA mutations tend to develop breast cancers at younger ages than people who do not have BRCA mutations²⁶

About 44% of women who inherit a harmful BRCA1 mutation will develop ovarian cancer by the age of 80.²⁶

About 17% of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by the age of 80.²⁶

People inherited with harmful BRCA mutations tend to develop ovarian cancers at younger ages than people who do not have BRCA mutations²⁶

Other cancers related to inherited harmful BRCA mutations Fallopian tube cancer, Peritoneal cancer, Prostate cancer, Pancreatic cancer²⁶

BRCA gene and its mutation

Normal BRCA genes encode proteins that repair DNA damage. This process helps prevent tumors from developing.⁴³
When BRCA genes are mutated, proteins that repair DNA damage may not be made, DNA damage may not be fixed properly. ⁴³
Cells with DNA damage continue to grow, divide, and develop additional genetic alterations that may result in cancer. ⁴³
This means that having a BRCA mutation could increase your risk of developing cancer.⁴³

BRCA mutations can either be inherited or acquired, and both male and female can be affected by the mutations and the cancers associated.

Germline mutations

When inherited from an individual's parents, they are classified as hereditary or germline mutations, and a cancer caused by an inherited gene mutation is called a hereditary cancer.⁴⁴

Somatic mutations

When not inherited from a parent and also not passed to offspring, they are classified as acquired or somatic mutations, and a cancer caused by an acquired gene mutation is called a sporadic cancer.^{44, 45}

Kind of BRCA mutations^{44, 45}

	Germline BRCAm	Somatic BRCAm
Hereditariness	Hereditary	Non-hereditary
Origin	Germ cells	Somatic cells, such as cancer cells
Sampling Method	Blood or buccal swap	Tumor biopsy

1 / 4

A mutation in either one of the two copies of the BRCA gene in a cell does not cause a problem, because the protein that is required for DNA repair can still be produced. When this control is lost as a result of a mutation in both copies of the same BRCA gene in the same cell, cancer may develop.³²

In general, the chances of having somatic or acquired mutations on both copies of BRCA gene are low. However, since germline BRCA mutation carriers (people born with a mutation in one copy of a BRCA gene and the other copy of that gene is normal) only need one more mutation in the other copy of BRCA gene to render the gene malfunction, they are more susceptible to develop cancer.³²

If a woman inherits a harmful BRCA1 or BRCA2 mutation, she has an increased risk of developing breast and/or ovarian cancer in her early age (before menopause) and in her lifetime as well.²⁶ In addition, she often has multiple, close family members who have also been diagnosed with these diseases.²⁶

BRCA gene mutations can be passed down to family members regardless of gender. This means that if you have an inherited BRCA mutation:⁴⁶

Your children have a 50% chance of inheriting the mutation.
Your siblings have a 50% chance of having the mutation.
There is a 100% chance that one of your parents has the mutation.

People with increased risk for a BRCA gene mutation

If your family history includes any of the following, you may be at increased risk for a mutation:⁴⁷

Multiple relatives had breast cancer
Relatives diagnosed with breast cancer before the age of 50
A relative had cancer in both breasts
A male relative had breast cancer
A relative with history of both breast and ovarian cancers
Any relatives had ovarian cancer
Of Ashkenazi Jewish ancestry and any relative had breast or ovarian cancer
A close relative with a known BRCA mutation⁴²

For people who may be at increased risk of having hereditary ovarian or breast cancer, the only way to know for certain if s/he has a germline (hereditary) BRCA1 or BRCA2 gene mutation is to have a genetic test.⁴⁷ A positive result in BRCA mutation test cannot tell whether or when an individual will develop cancer but can help people take steps to reduce their risk of diagnosing breast cancer and ovarian cancer at late stages.²⁶ People should meet with a genetic counselor and receive genetic counseling prior to genetic testing.⁴⁷

BRCA Testing

Several testing methods are now available to detect BRCA1 and BRCA2 mutations.⁴⁸ Genetic counseling is needed before and after a genetic test. Genetic counselors will usually conduct risk assessments based on your personal and family medical history.⁴⁸

Who should get tested for BRCA mutations?

If you are a woman with breast or ovarian cancer, you should consider BRCA mutation testing. Testing positive for a BRCA mutation determines whether or not you can receive certain targeted therapies.⁴⁶

For ovarian cancer patients, international guidelines such as those from NCCN,³⁷ SGO,⁴⁹ and ASCO¹⁶ recommend that they should be referred for BRCA mutation testing. This will help doctors to determine treatment options and patients to alerting families to their potential cancer risk if they are tested BRCA mutation positive.
For breast cancer patients with certain risk factors such as the following, it is also recommended that they should be tested for BRCA mutations.³⁷
- Diagnosed ≤45 years
- Diagnosed 46-50 years with an additional breast cancer at any age, or with ≥1 close blood relative with breast cancer at any age
- Diagnosed ≤60 years with triple-negative breast cancer (TNBC)
- Diagnosed at any age with ≥1 close blood relative with breast cancer diagnosed ≤50 years

If your family has a history of cancer, talk to your doctor about getting BRCA tested. If you have an inherited BRCA mutation, you could be at an increased risk of developing certain types of cancers, such as breast cancer and ovarian cancer.⁴⁶

Why get tested?

If you have cancer, knowing your BRCA status can help doctors decide on potential treatment options, such as a targeted therapy. It can also help inform others in your family about their own cancer risk.⁴⁶

If you do not have cancer, knowing your BRCA status will let you know if you are at an increased risk of developing certain cancers. From there, you and your doctor can screen for cancer more frequently or decide to take preventive action. Finding out that you have a BRCA mutation can also prompt other family members to get tested to see if they are at risk.⁴⁶

How is genetic testing done?

A blood or saliva sample is needed for testing germline BRCA mutations^{45, 60}, while a tumor biopsy is needed for somatic BRCA mutations.^{45, 61} The sample is taken in a laboratory, clinic, or hospital and then sent to a laboratory that performs the tests. It usually takes several weeks or longer to get the test results.²⁶

What do germline BRCA test results mean?

BRCA mutation testing can give several possible results: a positive result, a negative result, or an uncertain result.²⁶

A positive test result indicates that a person has inherited a known harmful mutation in BRCA1 or BRCA2 and, therefore, has an increased risk of developing certain cancers. However, a positive test result cannot tell whether or when an individual will develop cancer.²⁶ Knowing that you have a BRCA mutation can empower you to take action:

If you have cancer, ask your doctor how your BRCA status may affect your treatment plan and what treatment options would be best for your care. BRCA-mutated cancer may respond differently to certain cancer treatments, such as a targeted therapy.⁴⁶
If you do not have cancer, a positive BRCA mutation test result can help guide you on ways to reduce your risk of breast cancer and ovarian cancer and make plans to help detect cancer at an earlier stage.^{26, 46}
Inform your family – if you have a positive BRCA mutation test result, whether or not you have cancer yourself, may pass the mutation on to your sons and daughters.²⁶ Each child has a 50% chance of inheriting a parent’s mutation.²⁶ In addition, this will mean that each of your full siblings has a 50% chance of having inherited the mutation as well. ²⁶ Therefore, it is important for you to inform them to be tested to assess their cancer risk. Finding out early could prompt them to get cancer screenings regularly.⁵⁰

A negative test result can be more difficult to understand than a positive result because what the result means depends in part on an individual’s family history of cancer and whether a BRCA1 or BRCA2 mutation has been identified in a blood relative.²⁶

If one of your close relatives (first- or second-degree relative, such as a sibling or cousin) has tested positive for a BRCA mutation, your negative test result is considered a true negative. This means that you do not carry the BRCA mutation.⁵⁰
If no one in your family has tested positive for a BRCA mutation, but you have a family history of cancer, a negative result is not as straightforward. The possibility may include: ⁵⁰
1. You may not have inherited a BRCA mutation.
2. You may have a mutation in a gene other than BRCA1 or BRCA2: Your healthcare team may recommend more testing for other genetic mutations.
3. You may have an unknown BRCA mutation: A very small number of genetic tests can miss the BRCA mutation, and scientists continue to discover new BRCA mutations.

An uncertain result means you have a BRCA mutation that is not known to increase the risk of cancer. This occurrence is often referred to as a “genetic variant of unknown significance (Genetic Variant of Unknown Significance = VUS).”²⁶ As more research is done, scientists will learn more about these mutations and cancer risk.

If you have received this type of result, it is recommended that you contact a genetic counselor every 12 months to see if any additional mutations have been discovered.⁵⁰

BRCA myths

You may want to know the facts if you are considering testing. See the most common myths about BRCA mutations and the truth behind them

BRCA mutations are passed down the female line only.

Both men and women have a 50/50 chance to be inherited BRCA mutations. So, if someone has a BRCA mutation, there is a 50/50 chance that the mutation will be passed onto his/her child, regardless of whether the child is a son or a daughter. Therefore, looking into the family history of both the father and mother is important.⁵¹

BRCA mutations appear to "skip" a generation in some families.

It can be possible that no one in one generation with germline BRCA mutation gets cancer because the mutation does not necessarily translate into the development of cancer, but the mutation can still be passed down to future generations.⁵¹

I already have cancer - knowing my BRCA status will not change anything.

Even if you have cancer, knowing your BRCA status can help your doctor make informed decision of the most suitable treatment regimen (e.g. a targeted therapy) that fits your specific gene mutation profile and type of cancer. It can also help inform your family of their own potential cancer risk.⁵²

I am not at risk of developing cancer because I do not have a family history of cancer.

Family history is important, but it does not always predict cancer risk. A study showed that 47% of women with BRCA-mutated ovarian cancer have no relevant family history of cancer⁵². Thus, knowing your BRCA status helps to identify part of the risks of developing cancers.

Only young cancer patients need to have genetic counseling and BRCA tested, because cancers arising in the elderly are not hereditary.

BRCA mutations are not confined to women who present with a cancer such as ovarian or breast cancer at an early age. Studies showed that 71% of women with BRCA mutations are diagnosed at over 50 years of age.⁵⁹ Genetic testing can be used to confirm whether cancers are developed by inherited genetic mutation.⁵³

Men do not need to get BRCA tested because they cannot get breast or ovarian cancer.

Although it is true that men cannot get ovarian cancer, they can still get male breast cancer. In addition, they may also be at risk for the other cancers related to BRCA mutations such as prostate, and pancreas, if they are tested positive for a BRCA mutation. Men can also pass this genetic mutation on to their children, so finding out their BRCA mutation status can help inform the rest of their family about their own cancer risk.⁵²

16. Konstantinopoulous PA, et al. Journal of Clinical Oncology. 2020;38:1222-1245.

26. National Cancer Institute. BRCA Mutation: Cancer Risk and Genetic Testing. January 30, 2018. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet#q2. Accessed July 16, 2021.

32. BC Cancer Agency, Provincial Health Services Authority, Canada. Understanding Hereditary Breast & Ovarian Cancer – the BRCA genes. August 2014. Available at: http://www.bccancer.bc.ca/coping-and-support-site/Documents/Hereditary%20Cancer%20Program/HCP_GuidelinesManuals-UnderstandingHBOCBooklet.pdf. Accessed July 16, 2021.

37. NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. Version 2.2021.

42. The American College of Obstetricians and Gynecologists. BRCA1 and BRCA2 mutation. October 2017.

43. beBRCAware. BRCA Gene Mutation: A Closer look. Available at: https://www.bebrcaware.com/what-is-brca/brca-mutations.html. Accessed July 16, 2021.

44. Memorial Sloan Kettering Cancer Center. Hereditary Cancer & Genetics. Available at: https://www.mskcc.org/cancer-care/risk-assessment-screening/hereditary-genetics. Accessed July 16, 2021.

45. ID.BRCA. Make the Difference for Ovarian Cancer Patients. Start with BRCAm Testing.

46. beBRCAware. BRCA Guide: Navigating your journey. Available at: https://www.bebrcaware.com/content/dam/website-services/us/437-bebrcaware/3326949-ONCOLOGY%20NONBRANDED%20BeBRCAware.com%20BRCA%20Guide%20PDF.pdf. Accessed July 16, 2021.

47. Know:BRCA. Do You Know:BRCA?. Centers for Disease Control and Prevention Division of Cancer Prevention and Control. Available at: https://www.knowbrca.org/Learn/do-you-knowbrca. Accessed July 16, 2021.

49. Society of Gynecologic Oncology. SGO clinical practice statement: genetic testing for ovarian cancer. Available at: https://www.sgo.org/clinical-practice/guidelines/genetic-testing-for-ovarian-cancer/(Accessed on July 16, 2021.).

50. beBRCAware. BRCA Test Results: What Do They Mean? https://www.bebrcaware.com/i-know-my-brca-status/understanding-brca-test-results.html. Accessed July 16, 2021.

51. Ovarian Cancer Action. Busting the myths about BRCA. Available at: https://ovarian.org.uk/news-and-blog/blog/busting-myths-about-brca/. Accessed July 16, 2021.

52. beBRCAware. Top 5 Myths About BRCA Testing. Available at: https://www.bebrcaware.com/what-is-brca/top-5-brca-testing-myths.html. Accessed July 16, 2021.

53. National Cancer Institute. Genetic Testing for Hereditary Cancer Syndromes. Last updated: April 11, 2013. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet. Accessed July 16, 2021.

59. Song H, et al. The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. Hum Mol Genet. 2014;23(17):4703-4709. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119409/pdf/ddu172.pdf. Accessed July 16, 2021.

60. K. Bowles, S. Rajamani, S. Chen et al., Clinical validation of a buccal mouthwash collection and extraction protocol increases accessibility to BRCA 1 and BRCA2 genetic testing; (Abstract #1097). Presented at the 59th Annual Meeting of The American Society of Human Generics, 2009, Honolulu

61. Capoluongo E, Ellison G, López-Guerrero J, et al. Guidance Statement OnBRCA1/2Tumor Testing in Ovarian Cancer Patients. Seminars in Oncology 44 (2017) 187 -197. Available at: https://www.sciencedirect.com/science/article/pii/S0093775417300520. Accessed July 16, 2021.

Hereditary breast & ovarian cancer and brca mutation