BRCA mutation - breast cancer and genetics

The underlying cause behind about 5 to 10% of all breast cancers is an inherited mutation of two genes; namely the BRCA1 and BRCA2 genes (BRCA stands for ‘Breast cancer’).

These two genes are thought to be responsible for around 20% of familial cancers. This article briefly explains the link between breast cancer and genetics, and provides information about testing.

BRCA gene mutation: what does it mean?

A gene is a segment of the DNA code that we inherit from our parents. Genes have specific functions and some, like the BRCA1 and BRCA2 genes, produce tumour-suppressing proteins that help repair damage that can occur in the DNA during cell division. In doing so, these two genes protect us from cancer.

However, if either of these genes is mutated (the gene’s DNA code is changed), it may no longer be able to synthesise the tumour-suppressing proteins or these proteins may not function normally. When this occurs, repair of DNA damage may be suboptimal – the altered DNA may accumulate in cells and can lead to cancer.

Do BRCA gene mutations cause breast cancer?

Having a mutation in your BRCA genes does not mean that you’ll develop cancer but it significantly increases your risks of breast and ovarian cancer at a younger age. For instance, women with a faulty BRCA1 gene have a 60 to 90% risk of developing breast cancer at some point in their life, while those with a mutated BRCA2 gene have a 45 to 85% risk – the risk increases as the woman ages. Moreover, women with BRCA mutations who have had breast cancer also have a greater risk of developing another new breast cancer.

Can mutated BRCA genes be inherited?

Unfortunately, if either of your parents carries a mutation of the BRCA1 or BRCA2 genes, your risk of inheriting the faulty gene increases by about 50%. The effects of the mutation can be apparent even if your second copy of the gene (the one from your other parent) is normal.

How can you know if you have a faulty BRCA gene?

You may have defective BRCA genes if your mother, sister or close relatives have been diagnosed with breast cancer and/or ovarian cancer, especially at a young age. But the only way to know for sure if you’re carrying a mutated gene is to have a genetic test.

Testing for BRCA gene mutations

There are genetic tests that can investigate whether you have a mutation in either of your BRCA genes. In the NHS, genetic testing is usually carried out as a two-stage process.

The first stage involves a mutation search – a blood sample will be required from one of your close relatives who has been diagnosed with breast or ovarian cancer. The genetic material will then be extracted from the blood sample and the BRCA genes will be examined for a mutation. This mutation search, which can take a few weeks or months, is necessarily long since looking for an anomaly in a gene is the equivalent of trying to find a typo in an encyclopaedia.

If a mutation is discovered, genetic testing proceeds to the second stage which is known as a predictive test. In this stage, the researchers will test you for the presence of the specific mutation identified in your relative.

What do the test results mean?

If the result comes back positive, this implies that you are carrying a defective gene that may increase your risks of developing breast cancer. It also means that you may pass this defective gene on to your children even if you do not develop cancer yourself. And if you have siblings, there is a 50% probability that they have also inherited the faulty gene.

A true negative is a clear result: it means that, unlike your relative who was found to carry a defective gene, you are not a carrier of the mutation and hence, cannot transmit it to your children.

The result is less clear if no faulty gene was found during the mutation search, although the family history of the tested relative suggests the presence of a mutation. It could be that the genetic test has missed a known faulty gene (quite unlikely) or that your relative is carrying a mutation that has not yet been identified.

What if no mutation search can be done?

If your relative with breast cancer is deceased or is unavailable for the mutation search, you may still have a genetic test. However, it will not be as reliable and in the case where the results are negative, you will not know with absolute certainty that there is no gene mutation in your family.

Who should have the test?

In the UK, the National Institute for Health and Care Excellence (NICE) recommends genetic testing only for women with a high risk of developing breast cancer, such as those with:

• A close relative who has been diagnosed with breast cancer at a young age – the younger the relative, the more likely there is to be a mutation in the family.
• A close relative who has had cancer in both breasts.
• A family history of ovarian cancer.
• Male relatives diagnosed with breast cancer.

Where can you get genetic tests?

The NHS can offer you a free genetic test if you have a strong family history of breast cancer. For more information about the NHS gene testing labs, check out the UK Genetic Testing Network.

Private testing is also available in the UK – the cost will vary depending on the nature of the genetic test. To make sure you use a reputable company, ask for a referral from your doctor, breast specialist or genetic counsellor. A trustworthy private genetic lab will usually insist that the test be carried out through a healthcare professional who can walk you through the pros and cons of genetic testing, coordinate collection of blood samples and explain the results to you.

What if the tests are positive?

If a mutation has been found in your BRCA genes, you can opt for:

• Regular breast screening
  Screening can help discover cancer formation at a stage early enough to cure it. Breast ultrasound, mammograms and breast MRIs are usually carried out to detect abnormal breast changes.
• Surgery to remove your breasts and/or your ovaries
  Many women choose to have both breasts removed to reduce their risks of cancer. The operation can be followed by immediate reconstruction.
• Medicines that can reduce your risk of developing breast cancer
  Tamoxifen and Raloxifene are two drugs that can prevent breast cancer in highly susceptible women. NICE advises women at moderate to high risk of developing breast cancer to discuss with their doctor about taking either drugs for five years. In the future, other drugs may also be available, such as anastroloze, which may halve breast cancer occurrence in high-risk women.

For more information about BRCA genes, check out this in-depth guide from The Royal Marsden.