BreastGene – Genetic testing for breast cancer

BreastGene is a genetic test for breast cancer. It examines, in detail, the DNA code for 10 genes which are known to cause an increased risk of breast cancer. It is performed on a blood sample and, if possible, it is always more informative to also test a relative who has had breast cancer.

What is hereditary breast cancer?

Breast cancer is the most common cancer in the UK. Unfortunately, 1 in 8 women will develop breast cancer during their lifetime; with 80% being diagnosed after the age of 50. 1 in 868 men will also be diagnosed with breast cancer. This means that in the general population women have a 12-13% risk of breast cancer while men have a 0.1% risk. Most breast cancer occurs by chance, however approximately 5-10% is hereditary and in some families ovarian cancer can be genetically related to breast cancer. In families where breast cancer is hereditary it may be possible to find the genetic change (mutation) which is responsible for the cancer. This allows for appropriate cancer screening and risk-reducing options.

What are genes?

Genes are the body’s instructions and they determine how the body develops and is maintained. Some genes prevent cancer developing: if there is a mutation in one of these cancer genes, then the gene doesn’t work correctly and this causes an increased risk of cancer. Mutations in at least 10 genes can cause an increased risk of breast cancer and other cancers. However, we know that there are other genes which are also associated with breast cancer and research is attempting to understand these other genes.

How do I know if I am at risk?

Families with hereditary breast cancer generally show one or more of the following clues:

Several relatives with breast cancer

Breast cancer diagnosed before the age of 45

Bilateral breast cancer (cancer in both breasts)

Ovarian cancer

Increased frequencies of other cancers such as prostate and pancreatic cancer

Triple negative breast cancer

Male breast cancer

Jewish ancestry

How can genetic testing help?

Genetic testing can help determine the risk of cancer within a family and guide appropriate cancer screening. Depending on the specific genetic risk different screening tests can be arranged and risk-reducing strategies can be considered.

What is BreastGene?

BreastGene looks at 10 specific genes which cause an increased risk of breast cancer. 

How does the test work?

BreastGene is performed on a blood sample and it usually takes 3-6 weeks to obtain the results. In addition, dosage analysis is used to look for large deletions (missing parts) and duplications (extra parts) of the genes. However, no test is 100% and it is possible that someone could have a genetic mutation which is not detected by this test. It is most accurate to perform genetic testing on a family member who has had breast cancer so that a possible genetic cause can be found in the family. If this is not possible, genetic testing can be performed on someone who has not had cancer, although if the results are normal this will not be as informative.

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What will the test show?

1. A mutation is found in one of the genes which is   known to increase the risk of breast cancer. Increased screening and/or risk-reducing techniques will be recommended.

2. A genetic variation is found (known as a variant of uncertain significance or VUS), but whether or not this is the definite cause of cancer is unknown. Screening will be recommended based on the family history.

3. No mutation is found. It is possible that there may be an undetectable mutation or a mutation in a different gene. Cancer screening may still be beneficial.

What does it mean if I have a mutation?

If you have a mutation this means that you have an increased risk of breast cancer and possibly other cancers. Your exact risk(s) will depend on which gene mutation has been found. Extra screening and/or risk- reducing strategies will be discussed. It will also be possible to offer predictive testing to other people in your family to see if they also have the mutation.

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Hereditary Breast and Ovarian Cancer (HBOC):Mutations in BRCA1 & BRCA2 cause hereditary breast and ovarian cancer. In the general population 0.254% of Non-Jewish people and 2% of Ashkenazi Jewish people will have a BRCA mutation. The estimated cancer risks associated with BRCA mutations vary however; BRCA1 mutations are estimated to cause up to an 85% lifetime risk of breast cancer and up to a 60% risk of ovarian cancer. Men with BRCA1 mutations may have a slightly increased risk of male breast cancer as well as  approximately a 20% risk of prostate cancer. Women with BRCA2 mutations have up to a 90% lifetime risk of breast cancer and up to a 30% risk of ovarian cancer. Men with BRCA2 mutations have a 5-10% lifetime risk of developing breast cancer, and approximately a 40% risk ofprostate cancer. Individuals with BRCA2 mutations also have an increased risk of pancreatic cancer and possibly other cancers. Women with BRCA gene mutations should have breast MRI from age 30 years and annual mammogram from age 40 years.Ovarian cancer screening has not been shown to detect cancer sufficiently early to save livesand therefore some women may consider risk-reducing surgery. Men may benefit from prostate cancer screening with PSA testing. Occasionally, a baby willinherit two BRCA2 mutations and will therefore have the congenital condition known as Fanconi Anemia.

PTEN Hamartoma Tumor Syndrome / Cowden syndrome: Cowden syndrome causes bowel polyps, benign  skin lesions, benign breast disease, autism and other features. Individuals with Cowden syndrome   have an increased risk of bowel (9%), breast (85%), kidney (34%), thyroid (35%), and womb - also know as endometrial or uterine (28%) cancers as well as an increased risk of melanoma (5%). Colonoscopy, breast MRI, mammograms, renal MRI, skin examination and thyroid ultrasounds will be recommended. Risk reducing surgery may be considered.

Peutz Jeghers Syndrome (PJS): PJS causes polyps in the large and small bowel, as well as ovarian tumours and abnormal colouring of the skin, particularly on the lips in childhood. PJS causes an increased risk of bowel (39%), breast (45%), pancreatic (11%) and other cancers. Mammography, colonoscopy and other cancer screening tests will be recommended.

Hereditary diffuse Gastric Cancer (HDGC): HDGC causes a high risk of diffuse stomach cancer (83%) and lobular breast cancer (39-60%) as well as a probable increased risk of bowel cancer. Individuals with HDGC will be treated at a centre with expertise in the condition.  Increased breast screening with annual breast MRI and mammograms with be recommended. Some people also consider gastrectomy (removal of the stomach) due to the increased risk of stomach cancer) and bowel screening may be suggested.

Li Fraumeni Syndrome (LFS): Li Fraumeni syndrome is a relatively rare condition which causes a high risk of cancer in childhood and adulthood: approximately 1 in 5000 to 1 in 20000, people will have LFS. Li Fraumeni syndrome causes an increased risk of sarcomas, brain tumours, breast cancer (85% risk by age 60), adrenal cortical carcinomas and other cancers. Individuals with TP53 mutations have a 50% risk of developing some type of cancer by age 30 and a lifetime risk of up to 90%. Breast screening with MRI will be recommended. Individuals are also advised to avoid radiation as they have an increased radiation sensitivity.

ATM associated breast cancer: Approximately 1 in 200 people (0.5%) will carry a mutation in the ATM gene. Individuals with a mutation in the ATM gene have a moderately increased risk of breast cancer, as well as an increased risk of radiation-sensitivity. Increased breast screening is recommended. Rarely a baby may inherit an ATM mutation from their mother AND their father, in which case they will have the congenital condition called Ataxia- Telangiectasia (AT). AT causes uncontrollable movements (ataxia), immune defects, and an increased risk of leukaemia and lymphoma.

CHEK2: Mutations in the CHEK2 gene are found in 4% of families with hereditary breast cancer and cause a moderately increased risk of breast cancer as well as a possibly increased risk of bowel cancer. Very rarely individuals have been shown to carry 2 mutations in the CHEK2 gene which seems to cause a higher risk of breast cancer. Increased breast screening, and in some situations, bowel screening will be recommended.

PALB2: Mutations in PALB2 have been shown to cause an increased risk of breast cancer. The risk is  estimated to be approximately 35% although the risk is greater if there is a strong family history of breast  cancer (up to 57%) and our knowledge of PALB2 is rapidly increasing. Increased breast screening with mammography and MRI is recommended. PALB2 also causes a possible increased risk of pancreatic  cancer. Occasionally, a baby will inherit two 2 PALB2 mutations and will therefore have the congenital condition known as Fanconi Anemia.

NBN: Mutations in NBN are thought to cause a moderately increased risk of breast cancer. Increased breast screening with mammography is recommended.

How are these conditions inherited?

Genes come in pairs; we get one copy from our mother and one copy from our father. At present all known breast cancer syndromes are inherited in a dominant pattern. This means that if someone has a mutation in one copy of a gene then there is a 50% (1 in 2) chance that they will pass this onto their children. The risk of breast cancer can be inherited from either side of the family. 

Price

The cost for BreastGene is £1500 which includes pre and post-test genetic counselling.

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Financial issues

Some individuals may be concerned about difficulties obtaining insurance coverage following genetic testing. This does not need to be a concern as the Code on Genetic Testing and Insurance ensures that individuals do not have to disclose cancer predictive test results. More information can be found at https://www.abi.org.uk/globalassets/files/publications/public/genetics/code-on-genetic-testing-and-insurance_embargoed.pdf