BRCA-1 and BRCA-2 (Breast Cancer Gene 1 and 2) Tests
If a BRCA1/2 mutation is present in a family member; if you have a very strong family history of breast and/or ovarian cancer; if you have had a breast cancer under the age of 35 that is hormone receptor negative
A blood sample taken from a vein in the arm
The genetic code of two genes; the BRCA-1 and BRCA-2 genes will be analysed in detail to look for alterations (mutations) that are linked with an inherited tendency to breast and ovarian cancers. Most cancers will not be explained by such an alteration, but approximately 5% of all breast cancers are will have developed on the background of an inherited BRCA1/2 mutation. The inheritance of such a mutation is associated with a younger than average diagnosis of breast cancer (often, but not always below the age of 50, and sometimes as young as 30), so that a strong family history of young onset breast and ovarian cancer should alert the clinician to the possibility of a BRCA1/2 mutation. Note most clinical genetic services in the UK will have referral guidelines delineating the degree of family history and NICE has issued guidance about management of such families.
How is the sample collected for testing?
The test for BCRA mutations is done on a blood sample collected by needle from a vein in the arm. The test does not require surgical biopsy of breast or ovarian tissue.
Occasionally, alternative sample types might be possible, such as a mouth swab or spit sample.
Testing for BCRA mutations should be performed whilst under the care of a clinical genetics service. This is in order for patients to be fully informed and to allow appropriate consent for testing to be given.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
DNA is first extracted from the white blood cells in your sample. Your genetic code is the same in most of the cells in your body, so this is simply an easy route into exploring your genetic code. This is why a cheek swab or spit sample can also sometimes be used. The two genes BRCA1 and BRCA2 – which are located in different parts of the genetic code are then examined in detail to look for differences from the usual ‘sequence’ of chemicals along the code. A difference that alters the message this genetic code sends to the body is often known as a ‘mutation’. Different mutations in these genes in different families have been associated with the development of breast or ovarian cancer.
When is it requested?
Individuals with a strong family history of breast cancer or ovarian cancer may want to know if they have an inherited tendency to these cancers. Sometimes a very young onset of breast cancer may also indicate a likely BRCA1/2 gene mutation. For example a woman diagnosed with a triple negative breast cancer in her early 30s may have a BRCA1 gene mutation even if she does not have an obvious family history of cancer.
Note: the most useful prediction of risk from a BRCA1/2 test in an unaffected person is when a BRCA1/2 mutation has already been found in a relative with breast or ovarian cancer. Without this information, a negative BRCA1/2 test result is often not very informative. There are therefore two types of BRCA1/2 testing; ‘diagnostic’ and ‘predictive’ testing.
Diagnostic BRCA1/2 testing. This test is done in someone who has had a breast or ovarian cancer, usually in the context of a strong family history. It can give you information about chances of further cancers and can provide family members with the information to have a predictive test.
Predictive BRCA1/2 testing. This test is done in an unaffected relative of someone who is known to have a BRCA1/2 gene mutation. If you are a child or sibling of this person there will usually be a 50:50 (1 in 2 or 50% chance) that you have, or have not, inherited the mutation.
Such testing may be useful to help you decide whether to take steps that may prevent breast or ovarian cancer from developing, or may pick it up at an earlyat a more treatable stage. There are a complex range of options available, ranging from more frequent mammograms to surgical removal of the organs at risk and you should discuss these in detail with a clinical genetics professional before deciding whether testing would be helpful or right for you. Your GP can refer you to your local clinical genetics service. (see "Is there anything else I should know?" below).
What does the test result mean?
Since there are hundreds of possible mutations of BRCA genes, test results must be interpreted by taking into account a person’s personal and family history. A genetic health professional should explain the meaning of the results and offer advice to the individual and to other family members about options for decreasing risk. Such advice should be offered both before testing takes place and after receiving test results.
I’ve been told my test result is uncertain, what does this mean?
There are two situations where a test result does not give a clear ‘yes/no’ positive/ negative answer:
1. You have a strong family history of breast/ovarian cancer but a BRCA1/2 mutation has not been found in your family (this might be because there is no-one available to test, or because someone has been tested but no mutation has been found). In this case, a negative BRCA1/2 test does not help you to clarify your risks. The test might be negative because you have not inherited a mutation that is present in your family, OR the test is negative because BRCA1/2 does not explain your family history. If this is the case we cannot say whether you have got the same familial risk or not.
2. Your BRCA1/2 test result shows a variant of uncertain significance (‘VUS’) This means that there is a variation in your BRCA1/2 genetic code, but this variation may be normal (like genetic code variations that determine eye colour or hair curliness for example) or disease related. It will be important to have your result regularly reviewed as more evidence about genetic variations is gathered.
Is there anything else I should know?
Your test results can affect other family members. When one member of a family is tested for BRCA mutations, issues often arise about how to share this information with other family members. Most people will want to help their family members, and may indeed only ask for testing in order to do so, but sometimes you may have lost touch with family members to whom the result may be relevant, or find it too difficult to tell them yourself. Your local clinical genetic service will be able to help you with this.
If the BRCA test is positive, what are my treatment options?
If the BRCA test is positive, we consider you to be at increased risk of developing breast and or ovarian cancer. You will have a detailed discussion with a health professional about the latest evidence for certain check-ups (e.g., mammography, MRI scans) or preventative options such as surgical removal of the ovaries or breasts.
If the test is positive, how likely am I to get breast or ovarian cancer?
Your risk will depend on your family history and will need to be determined by a genetic counsellor. Research studies have reported that of every 1000 women positive for BRCA mutations, between 330 and 423 will develop breast cancer by age 50 and between 70 and 90 will develop ovarian cancer by age 50. The risk increases with age.
If the test is negative, how likely/unlikely am I to get breast or ovarian cancer?
Every woman in the general population has a chance of developing breast or ovarian cancer, and a negative BRCA1/2 test does not change this. However, we also know that a certain proportion of women with a BRCA1/2 gene mutation will never develop breast or ovarian cancer. Approximately 20% of such ‘carriers’ will never develop breast cancer, and 40-90% will never develop ovarian cancer.
Should men be tested for BRCA1/2?
It depends on your family circumstances. Men have a much lower chance of cancer if they have a BRCA1/2 mutation because they have less breast tissue and no ovarian tissue. However, the risk of prostate cancer is increased from the age of 40 onwards with some mutations, particularly BRCA2 ones, and the risk of breast cancer is increased in men who have a BRCA2 mutation (the lifetimes risk of breast cancer for men with a BRCA2 mutation is approximately 5-10%). It’s important to note though that the gene mutations are passed down the male or female line equally, even though the chances of cancer are different depending on your gender. This means that it’s always important to think about a family history of breast and ovarian cancer on a paternal side of a family also. Men may not be aware they have a BRCA1/2 mutation but they can pass it onto their daughters who may then be at increased risk.
Where can I get this test?
You can ask your doctor for a referral to your local clinical genetics service. They will be able to discuss with you the advantages and disadvantages of testing and help you decide what is best for you. The blood sample will be sent to a laboratory that specialises in genetic testing.