Breast cancer genes
Breast cancer genes

Why carrying inherited faulty genes increase risk
There have to be a number of mistakes in a cell's genetic code before it becomes cancerous. Doctors call these mistakes '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 cause cancer. This doesn't mean you will necessarily get cancer. But it will mean that you are more likely to than the average person. Faults in some breast cancer genes increase your risk of cancer because they are genes that normally protect cells from cancerous changes.

How much breast cancer genes increase your risk
The first breast cancer gene faults to be found were BRCA1 and BRCA2. These faults don't mean you have cancer, or you definitely will get cancer but 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, TNRC9, MAP3K1 and LSP1. No tests are available to find 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.

What lifetime risk means
Lifetime risk can be quite difficult to understand. 1 in 9 women in the UK will develop cancer during their lifetime. But the risk is small in younger women and and increases as they get older. Women with a faulty breast cancer gene will 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 carry a breast cancer gene.

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

How genetic tests work
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. Then the researchers look for that same gene fault in you. They are more likely to find the fault if they know what to look for.

Some labs can do a test on 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 genetic tests can miss the fault. So, if your relative with breast cancer’s test is negative, this only means they didn’t find a gene mutation – not that there definitely isn’t one there. There is more about the reliability of gene testing further down this page.

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 they 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 be tested for one of these mutations. Because the testers know what to look for, it is possible to have this test without a living relative with breast cancer.

Who should be tested
In the UK, guidelines published by NICE (the National Institute for Health and Clinical Excellence) say that women should only be referred to a specialist genetics services for gene testing if they 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. There are many different family situations they outline 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've had breast cancer
If there is also ovarian cancer in the family
The affected family members you are 'counting' towards your risk 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 on to a specialist genetics service. There, they 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 whether you are going to do anything about it or not if you get a positive result. 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 for you about 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.

About the test
There are one or two things to think about before asking for a test

How do you feel about being tested
What does the result really mean?
What would you do if the result was positive?
Before you ask for gene testing, think about what it may mean for you. What will you do about the result? How will you feel? Would you rather not know? Would you consider having both breasts removed to prevent breast cancer?

There are also one or two things to know about the test. If you haven't had breast cancer, in order to be tested in the first place, you usually need to have a relative with a known gene mutation. The lab staff can then look for exactly the same gene fault in your genetic code and tell you whether you have inherited it or not.

If you haven't had a relative tested already, but you have a living relative with breast cancer, they usually have to be tested before you can be tested. But unfortunately, this still isn't straightforward. There are many different gene mutations. The genetic code is very long and a gene fault could be in many different places. Having a living realtive who can be tested makes it much more likely that the genetic fault will be found. But even this is not 100% accurate.

How reliable the test is
As we’ve said, it is best if a woman in your family who already has breast cancer is tested first to try to find a gene fault. Then, if they find one, they will look for the same fault in you.

Some NHS labs in the UK don’t check the whole gene. Generally, they check about 60% of it, although this varies between labs. To keep the ‘spelling mistake’ example, this is like looking for a single spelling mistake in the first 12 chapters of a 20-chapter book, but ignoring the last 8 chapters. So a negative result means they haven't found a gene fault, but it doesn’t mean there definitely isn’t one there. Across the country, the labs find a gene fault in about 2 out of 10 women having this test. So in 8 out of 10, the test is inconclusive. Some labs check the whole gene and this is much more accurate. 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 100% gene testing privately. You have to send a blood sample to the USA. It is still best to have a living relative with breast cancer so that they can be checked for all the commonest 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, they won't be able to tell you whether there is a gene mutation in your family or not. So you will have paid out a couple of thousand pounds and won't know any more than you did before.

Do be careful when finding private medical services on the web. There are some charlatans out there, particularly advertising on the internet. One reliable company is called 'Myriad' - they developed the test originally. Even if you are sure the company you've picked is reliable, you really need to talk this over with a breast specialist or genetics specialist before going ahead. Do remember that most women who get breast cancer do not have breast cancer gene faults. And you must be sure you've thought about how the result will affect you.

The 2004 NICE guidelines said the UK should aim for 100% gene testing instead of 60%. The UK Government has said it will put more resources into improving gene testing in this country and in time all labs should be doing 100% testing on the NHS. But we don't know when that will happen just yet.

The result
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 gene fault in you 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 as was found in your relative. A very rare possibility is that you could carry a different breast cancer gene mutation, but this isn't very likely.

Remember - if you are the first person in your family to ask for a breast cancer gene test, you must usually have a relative with breast cancer tested first. If that relative has a negative result, that means the lab didn’t find a gene fault in their sample. Unfortunately, that doesn't mean there isn’t one - just that they didn’t see one in the bit of the gene sequence they examined.

What to do if you have a positive test result
There are 3 options if you carry a known breast cancer gene

Have regular breast cancer screening
Have surgery to remove your breasts
Join a prevention trial
Screening will increase the chance of a breast cancer being picked up early enough to cure it. Having surgery is an option. Some women choose to have both breasts removed and immediate breast reconstruction. But it does not completely rule out the risk of breast cancer. It is possible that there are cells somewhere else in your body that could develop into breast cancer, although this is relatively rare.

You may also be advised to have your ovaries removed. Unfortunately, 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 age 75. This is the maximum risk. The actual risk will vary from family to family, depending on how often the gene fault shows up (called gene penetrance).

A clinical trial called IBIS1 has been looking into using tamoxifen to prevent breast cancer starting 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 the drug.

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.

CancerHelp UK
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Cancer Research UK
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