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Did you know breast cancer and ovarian cancer can be inherited?

Angelina Jolie discovered she carries a faulty copy of the BRCA1 gene. Therefore, she had made a difficult decision to have surgery to prevent breast cancer.

Hereditary Breast and Ovarian Cancer & BRCA mutation

Cancer arises when cells become uncontrolled while growing and dividing. This loss of control is due to genetic changes in the cells.

Hereditary breast and ovarian cancer (HBOC) syndrome refers to an inherited increased risk of breast, ovarian, pancreatic and prostate cancer, and it is most commonly linked to an inherited genetic change or in other words, a mutation in our BRCA genes. About 5 – 10% of breast cancers and 14 – 24% of ovarian cancers are found to be hereditary.1-4

Understanding BRCA gene5

All of us have 2 sets of BRCA genes, BRCA1 and BRCA2. BRCA stands for BReast CAncer susceptibility gene. BRCA genes are tumour suppressor genes, which means that these genes have an important role to keep our cells in good condition. However, when these genes are mutated, they lose their ability to protect the cell and this increases the risk of developing breast and ovarian cancer.

Other cancers which may be caused by a faulty BRCA gene include fallopian tube cancer, peritoneal cancer, prostate cancer and pancreatic cancer.

BRCA mutations6

BRCA1 location

Breast Cancer

Ovarian Cancer

BRCA2 location

Breast Cancer

Ovarian Cancer

There are two types of BRCA mutations7

Germline BRCA mutations

This type of mutation is inherited from an individual’s parents.
They are often called hereditary mutations and can be inherited by the children.

Somatic BRCA mutations

This type of mutation is not inherited from an individual’s parents, but rather occurs randomly over their lifetime due to other risk factors. They are often called acquired mutations and cannot be inherited by the children.

Testing for BRCA

Who should test for BRCA?

If you have been diagnosed with breast or ovarian cancer, you should consider BRCA mutation testing. Testing positive for a BRCA mutation could mean that you may be eligible for certain targeted therapies such as a PARP inhibitor.

In many countries, BRCA testing is routinely performed for patients newly diagnosed with breast and ovarian cancer as recommended by guidelines. If your family has a history of cancer, speak to your doctor about getting a BRCA test.

For ovarian cancer patients:

International guidelines such as those from NCCN, SGO and ASCO recommend BRCA mutation testing for all epithelial non-mucinous ovarian cancer patients.8-11

For breast cancer patients:

It is recommended to test for BRCA mutation based on the following risk factors:12

  • Ovarian cancer (epithelial non-mucinous ovarian cancer)
  • Breast cancer in patient diagnosed ≤ 45 years old
  • Two primary breast cancers, both diagnosed ≤ 60 years old
  • Triple-negative breast cancer, diagnosed ≤ 60 years old
  • Male breast cancer
  • Breast cancer plus parent, sibling or child with any of the above criteria
Why should you test for BRCA?

If you have cancer, knowing your BRCA status can help you and your doctors decide on the best treatment option. It can also help inform others in your family about their cancer risk and allow them to take a proactive approach to manage their risk of developing cancer.

If you are a family member who does 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.

How is it done?

A blood or saliva sample is needed for testing hereditary BRCA mutations, while a tumour tissue is needed for testing somatic BRCA mutations. Tumour tissue is usually obtained from the surgery or biopsy performed if you have been diagnosed with cancer.

The sample taken is then sent to a laboratory that performs the tests. It usually takes 2-4 weeks to get the test results.

A tumour BRCA test can detect both germline and somatic mutations, however it does not differentiate between them. This type of test can be useful in deciding your treatment options.13

A blood or saliva BRCA test detects only germline BRCA mutations.
Therefore, it is useful in informing whether you have an inherited BRCA mutation.14

Ideally, both tumour and germline BRCA testing should be performed and depending on the family history and therapeutic indications.

What do you need to know about the results?15

BRCA mutation testing can give several possible results:

Positive Result

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 inform on whether or when an individual will develop cancer.

Knowing that you have a BRCA mutation can empower you to take action:

1.
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.
2.
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.
3.
Inform your family – if you have a positive BRCA mutation test result, whether or not you have cancer yourself, you may pass the mutation on to your sons and daughters. Each child has a 50% chance of inheriting a parent’s mutation. In addition, each of your full siblings has a 50% chance of carrying the mutation as well. 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.
Negative Result

A negative test result means that the BRCA genes tested have no mutations.

1.
If no one in your family has tested positive for a BRCA mutation, but you have a family history of cancer, a negative result may mean that:
  • You may not have inherited a BRCA mutation.
  • You may have a mutation in a gene other than BRCA1 or BRCA2: Your healthcare team may recommend more testing for other genetic mutations.
  • 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.
2.
If one of your close relatives (parent, siblings, children) 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.
Uncertain Result

An uncertain result means you have a BRCA genetic change but the impact of this change to the risk of cancer is unknown.

This is often referred to as a “genetic variant of unknown significance (VUS).” As more research is done, scientists will learn more about these genetic changes and the cancer risks associated with them.

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 information has been discovered which may lead to the reclassification of these results.

References
  1. Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, Lee DS, Lee SY, Yoon SY, Lim J, Lau SY, Decker B, Pooley K, Dorling L, Luccarini C, Baynes C, Conroy DM, Harrington P, Simard J, Yip CH, Mohd Taib NA, Ho WK, Antoniou AC, Dunning AM, Easton DF, Teo SH.J Med Genet. 2018 Feb;55(2):97-103. doi: 10.1136/jmedgenet-2017-104947. Epub 2017 Oct 9.
  2. Modan B, Hartge P, Hirsh-Yechezkel G, et al: Parity, Oral Contraceptives, and the Risk of Ovarian Cancer among Carriers and Noncarriers of a BRCA1 or BRCA2 Mutation. 345:235-240, 2001
  3. Alsop K, Fereday S, Meldrum C, et al: BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 30:2654-63, 2012
  4. Li A, Xie R, Zhi Q, et al: BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. Gynecol Oncol 151:145-152, 2018
  5. Gudmundsdottir, K, and A Ashworth. "The Roles Of BRCA1 And BRCA2 And Associated Proteins In The Maintenance Of Genomic Stability". Oncogene, vol 25, no. 43, 2006, pp. 5864-5874. Springer Science And Business Media LLC, doi:10.1038/sj.onc.1209874.
  6. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 2017; 317(23):2402-2416.
  7. "Germline And Somatic Mutations: What Is The Difference?". ONS Voice, 2020, https://voice.ons.org/news-and-views/germline-and-somatic-mutations-what-is-the-difference.
  8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Genetic/Familial High-Risk Assessment: Breast and Ovarian. V.2.2019. ©National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed August 13, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.
  9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer V.2.2018. © National Comprehensive Cancer Network, Inc 2018. All rights reserved. Accessed August 28, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.
  10. Lu KH, et al. J Clin Oncol. 2014;32(8):833-840.
  11. SGO Web site. http://www.sgo.org/clinical-practice/guidelines/genetic-testing-for-ovarian-cancer/. Accessed August 16, 2018.
  12. Clinical practice guidelines 2019 Management of Breast Cancer Third Edition MOH/P/PAK/432.19(GU)-e.
  13. Endris V, et al. Virchows Arch. 2016;468(6):697-705
  14. Capoluongo E, et al. Seminars in Oncology. 2017;44:187-197.
  15. "What Do Your BRCA Test Results Mean? | Bebrcaware". Bebrcaware.Com, 2020, https://www.bebrcaware.com/i-know-my-brca-status/understanding-brca-test-results.html.
Enquiries? Contact our genetic counsellor