Breast cancer genes

There have to be a number of mistakes in a cell's genetic code before it becomes cancerous. Doctors call these mistakes faults or mutations. Most of these gene mutations develop during our lifetime - either because of substances we come into contact with that cause cancer. Or because of mistakes cells make when copying their genetic code before dividing into two new cells. Most of these abnormal cells die or are killed off by your immune system. It usually takes many years to gather enough genetic mistakes so this is one of the reasons cancer is generally more common as we get older.

But it is possible to be born with a gene fault that may increase the risk of cancer. This doesn't mean you will definitely get cancer. But it means that you are more likely to develop cancer than the average person.

The first breast cancer gene faults to be found were BRCA1 and BRCA2. Women with these genes have a 50 to 80% chance of getting breast cancer in their lifetime. We now know of other genes that significantly increase a woman's risk of breast cancer. They are called TP53 and PTEN. Genetic tests are available to women with a high risk of having changes in their BRCA1, BRCA2, TP53 or PTEN genes.

Researchers have found other common genes that can slightly increase a woman's risk of developing breast cancer. These are called CASP8, FGFR2, TNRCP, MAP3K1, rs4973768 and LSP1. No tests are available for these genes yet.

Rare genes that can also increase breast cancer risk slightly include CHEK2, ATM (ataxia telangiectasia mutated), BRIP1 and PALB2. No tests are available for these genes yet.

Lifetime risk can be quite difficult to understand. 1 in 8 women in the UK will develop breast cancer during their lifetime. But the risk is small in younger women and increases as they get older. Women with a faulty gene have a higher risk of developing breast cancer than people of the same age. But if you are 30, your risk of breast cancer is going to be much lower than if you are 80, whether or not you have a faulty gene.

There is detailed information about definite risk factors for breast cancer, including what is meant by having a family history, in this section of CancerHelp UK.

It is only possible to have a test for BRCA1, BRCA2, TP53 or PTEN if you have a strong family history of breast cancer. Most people also need to have a living relative with breast cancer. This is because looking for a gene fault is a bit like looking for a single spelling mistake in a very long book. Your relative has to be tested first to try to find out which fault on the breast cancer genes might run in your family. This is called the mutation search and can take a few months or more. If a faulty gene is found the researchers can then look for that same gene fault in you. This is called predictive testing.

Some labs can test the genes without having blood from a living relative, but this is less likely to find the fault. It is important to remember that no test is 100% accurate and any gene test can miss the fault. So, if your test is negative, this only means they didn’t find a gene mutation - not that there definitely isn’t one there. 

With particular groups of women, there are very common specific gene faults. Ashkenazi Jewish women tend to have one of 3 very particular gene mutations. Specialists in breast cancer gene testing know where these mutations are in the gene. So it is much easier to check to see if you carry one of them. If you are Ashkenazi Jewish, you can have tests for these mutations.

In the UK, guidelines published by the National Institute for Health and Clinical Excellence (NICE) say that women should only be referred to a specialist genetics services for gene testing if they are likely to have a high risk of developing breast cancer. They define a high risk as having a 1 in 3 chance of getting breast cancer at some point in your life. Or a greater than 1 in 12 chance of getting breast cancer before the age of 50. The guidelines outline the different family situations that could mean you are at high risk. Generally, they look at

• The age your relatives were diagnosed with breast cancer (the younger they are, the more likely there is to be a faulty gene in the family)
• Whether anyone had cancer in both breasts
• If there are men in your family who have had breast cancer
• If there is also ovarian cancer in the family

The affected family members must be close, blood relatives of yours and must all be from the same side of the family (so either your mother's relatives OR your father's). You can download the public information on familial breast cancer from NICE or ask them to send you a copy in the post.

To get a genetic test, you need to ask your GP for a referral to a specialist breast clinic. If they think you probably do have a high risk of breast cancer, they will refer you to a specialist genetics service. There, the staff will talk to you about your risk and discuss the test with you. The test result takes a few weeks, sometimes longer, to come back.

Before you decide whether or not to go ahead with the test, the staff in the clinic will make sure that you have good information to take away, read, and think about. Having a test can have a big impact on you and other members of your family. The clinic staff will try to answer all the questions you have about the test. There’s no rush and you can take as long as you need to make up your mind whether to go ahead or not.

Even if you know it is possible, finding out that you have a high risk of breast cancer is still likely to come as a shock. You need to be sure that you want to know the test result before you go ahead. And that you will be able to decide what you will do if you have a faulty gene. Everyone is different and there is no right or wrong way to feel about this. The important thing is that you feel you have been given enough information to make the right choice about whether to have the test. Talk it over with a good friend or relative. Or if you feel you need to talk with your genetics specialist again, get back in touch with them.

You have to give a blood sample. You can find information about NHS gene testing labs on the UK genetic testing network website. You can look on their database to see which services are offered by labs close to you.

You can have gene testing privately. It is still best to have a living relative with breast cancer so that they can be checked for all the most common gene faults first. You can have a test without having a living relative with breast cancer tested, but the result won't be as reliable. If it comes back negative, you still don't know for sure whether there is a gene mutation in your family or not.

Do be careful when finding private medical services on the web. There are some charlatans advertising on the internet. One reliable company is called Myriad - they developed the test originally. Even if you are sure you have found a reliable company, you really need to talk this over with a breast specialist or genetics specialist before going ahead.

The most accurate way to find a faulty gene is to have a test after a faulty gene has already been found in one of your relatives who has breast cancer. The genetics lab will then look for this specific fault in your genes and can say definitely whether it is there or not.

A positive result means you carry a known breast cancer gene. As we have seen, this means about a 50 to 80% chance of developing breast cancer by the end of your life.

A negative result means you do not carry the same gene fault that was found in your relative and so you have the same risk of cancer as other people in the population. A very rare possibility is that you could carry a different breast cancer gene mutation, but this is unlikely.

There are 3 options if the test shows that you carry a known breast cancer gene

• Have regular breast cancer screening
• Have surgery to remove your breasts (and possibly your ovaries)
• Join a prevention trial

Have regular breast cancer screening

Screening increases the chance of a breast cancer being picked up early enough to cure it. Depending on your age, you may be offered regular mammograms, breast ultrasound or breast MRI scans.

Having surgery to remove your breasts (and possibly ovaries)

Having surgery is an option. Some women choose to have both breasts removed and immediate breast reconstruction, which greatly reduces the chance of breast cancer but does not completely reduce the risk. You may also be advised to have your ovaries removed because some breast cancer gene faults increase the risk of ovarian cancer too. As many as 2 out of 3 women who carry the BRCA1 or 2 genes will get ovarian cancer by the age of 75. A 2009 overview looked at all the studies that have been done into removing the ovaries and fallopian tubes to reduce breast cancer risk in women who have BRCA gene changes. The overview showed that this surgery reduced the risk of breast cancer in these women by 50%. 

Prevention trials

A clinical trial called IBIS1 has been looking into using tamoxifen to prevent breast cancer in women with a strong family history. The women in this trial took tamoxifen for 5 years. The results show that tamoxifen lowers breast cancer risk by about a third in high risk women. And we now know that the benefit carries on for at least another 5 years after women stop taking tamoxifen. Tamoxifen does have side effects, but these nearly all go as soon as women stop taking it. A further development of this trial, IBIS2 started in 2003. This trial is looking at whether another type of hormone drug, anastrozole (Arimidex) can prevent breast cancer in women at high risk. You can find details of the trial on our clinical trials database. Pick 'breast' from the dropdown menu. Or you can type 'ibis' into the free text search box.

There is a little more information about faulty breast cancer genes in the CancerHelp UK page about research into finding and preventing breast cancer. You can also go to the Cancer Research UK welcome page and search for 'breast cancer genes' to find information on all our websites.

If you would like to check your own breast or ovarian cancer risk you can use the OPERA online interactive tool.