Genetic Testing for Breast Cancer Explained

Genetic testing gives people the chance to learn if their family history of breast cancer is due to an inherited gene mutation.

Most women who get breast cancer do not have an inherited gene mutation. Five to 10 percent of breast cancers in the U.S. are linked to an inherited gene mutation

Why Faulty Genes Increase Risk?

A cell needs to have a number of mistakes in its genetic code before it becomes cancerous. Doctors call these mistakes faults or mutations. Most of these gene mutations develop during our lifetime.

They can occur due to substances we come into contact with that cause cancer. Or they can happen because of mistakes that 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 that cancer is generally more common as we get older.

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

Types of faulty genes

The first breast cancer gene faults to be found were BRCA1 and BRCA2. Between 45 and 90 out of every 100 women carrying BRCA genes will get breast cancer at some point in their lives.

This means that they have between 45% and 90% lifetime risk of cancer. These genes also increase breast cancer risk in men.

We 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 these genes

  • BRCA1
  • BRCA2
  • TP53
  • PTEN genes

Researchers have found other common genes that can slightly increase a woman’s risk of developing breast cancer. No tests are available for these genes yet but they include

  • CASP8
  • FGFR2
  • TNRCP
  • MAP3K1
  • rs4973768
  • LSP1

Rare genes that can also increase breast cancer risk slightly include

  • CHEK2
  • ATM (ataxia telangiectasia mutated)
  • BRIP1
  • PALB2

No individual tests are available for these genes yet. But if you are having a test for the BRCA genes they may find changes in one of these genes.

What lifetime risk means

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 in this section, including what is meant by having a family history.

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 needs 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 weeks or months.

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 means that the tests didn’t find a gene mutation. It doesn’t necessarily mean that there 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.

Who should have tests

In the UK, guidelines published by the National Institute for Health and Care 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.

NICE defines 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 read the public information on familial breast cancer on the NICE website.

Getting a test

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 you also need to be sure 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, you can get back in touch with them.

Having a test

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.

It is important to be careful and make sure that you use a reputable company when finding private medical services on the web. Even if you are sure that you have found a reliable company, you really need to talk this over with a breast specialist or genetics specialist before going ahead.

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 fault in your genes and can say definitely whether it is there or not.

A positive result means that you carry a known breast cancer gene. As we have seen, this means that you have an increased risk of breast cancer.

A negative result means that you do not carry the same gene fault that was found in your relative. So you have the same risk of cancer as other people in the population.

A very rare possibility is that you could have a different breast cancer gene mutation, but this is unlikely.

Weighing the risks and benefits of BRCA1/2 testing

Although testing for a BRCA1/2 gene mutation just requires a blood test, the risks and benefits should be considered before testing. There are potential physical, emotional and financial impacts of knowing your genetic status.

Talking with your health care provider about your risk of a BRCA1/2 mutation

If you have concerns about your risk of having a BRCA1/2 gene mutation, talk with your health care provider. He/she can help you understand your risk and can refer you to a genetic counselor.

There are a few online tools to help you talk with your provider about your risk of a BRCA1/2 mutation and your risk of breast cancer.

Please keep in mind these tools cannot tell you whether or not you have a BRCA1/2 mutation or if you will get breast cancer. Rather, they may help you talk with your provider or a genetic counselor about these risks.

Testing for BRCA1/2 mutations

In most cases, testing is first done on the person with breast or ovarian cancer. If no mutation is found, the cancer was probably not due to a BRCA1/2 mutation and there is no need to test other family members. If a BRCA1/2 mutation is found, other family members can be tested for the specific mutation.

It is not likely that all family members will have the mutation. For example, if your mother has a BRCA1 or BRCA2 mutation, there is only a 50 percent chance that you will also have a mutation (you get half of your genes from your mother and half from your father).

If your family members with breast cancer or ovarian cancer are deceased or are not willing to be tested (or if your family medical history is unknown), a genetic counselor can help you decide whether it would be useful for you to have BRCA1/2 testing.

Testing for other gene mutations

Of the genes linked with breast cancer, BRCA1 and BRCA2 are the most well-understood. When a person is found to have a mutation in one of these genes, there are special recommendations for breast cancer screening, risk-lowering options and care.

So, genetic testing for BRCA1/2 mutations can affect a person’s medical care.

Inherited gene mutations in some other genes such as p53, CHEK2, ATM and PALB2, also increase breast cancer risk. Testing for some of these mutations exists. However, these gene mutations are rare and little is known about how to tailor medical care to people with these mutations.

So, although testing for multiple gene mutations is becoming more available, health care providers do not yet know how to use much of the information from these tests.

If your family members with breast cancer or ovarian cancer are deceased or are not willing to be tested (or if your family medical history is unknown), a genetic counselor can help you decide whether it would be useful for you to have testing for other inherited gene mutations.

At-home genetic testing

You may have seen ads for at-home genetic testing kits. These kits are not recommended for assessing breast cancer risk. The U.S. Food and Drug Administration, U.S. Federal Trade Commission and Centers for Disease Control and Prevention all caution against the use of at-home testing kits.

The results of any genetic test should be interpreted by a trained health care provider or genetic counselor

If you have a positive test result

There are options if the test shows that you have a known faulty breast cancer gene. You can

  • Have regular breast cancer screening
  • Have surgery to remove your breasts (and possibly your ovaries)
  • Take medicines to lower your risk
  • 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 surgery to create new breasts (breast reconstruction).

This greatly reduces the chance of breast cancer but does not completely reduce the risk. This type of surgery is called prophylactic mastectomy or preventive mastectomy.

Your medical team may also advise you to have your ovaries removed. 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%. This operation is called prophylactic oophorectomy.

Take medicines to lower your risk

Another option is taking a drug to lower your risk of developing breast cancer. Tamoxifen is a drug that has been used to treat breast cancer for more than 35 years. It works by stopping oestrogen from triggering hormone receptors in breast cancer cells.

Raloxifene is a drug used to treat osteoporosis. Research has found that these drugs can also help to prevent breast cancer in women at high risk.

The National Institute for Health and Care Excellence (NICE) has approved tamoxifen and raloxifene for women at high or moderate risk of developing breast cancer.

NICE says that women with an increased risk should talk to their doctor about taking either tamoxifen or raloxifene for 5 years as a possible way of lowering their risk. Both of these drugs have side effects including increasing the risk of developing blood clots and strokes.

So, NICE do not recommend them if you have had a blood clot or are at risk of developing one. Tamoxifen also slightly increases the risk of womb cancer.

The IBIS 2 trial reported in 2013 that taking anastrozole (Arimidex) for 5 years can reduce the risk of developing breast cancer by 50% in women at high risk.

There is information about research looking into drugs which may prevent breast cancer on the page about research into preventing and diagnosing breast cancer.

Making a decision about what to do is not easy. It can help to find out as much information as possible about your risk and the different options as well as the pros and cons of each.

Genetic testing gives people the chance to learn if their family history of breast cancer is due to an inherited gene mutation.

Most women who get breast cancer do not have an inherited gene mutation. Five to 10 percent of breast cancers in the U.S. are linked to an inherited gene mutation.

Genes and gene mutations

Every cell in your body contains genes. Genes contain the blueprints (genetic code) for your body. For example, they contain the information that determines the color of your eyes. They also contain information that affects how the cells in your body grow, divide and die.

The information in your genes is passed on (inherited) from both your mother and your father. And, you can pass this information on to your children, both your daughters and sons.

Some changes in the genetic code that affect the function of the gene are called mutations. Mutations are rare. However, just as with other information in genes, mutations can be passed on from a parent to a child.

Some inherited gene mutations increase breast cancer risk. BRCA1 and BRCA2 (BReast CAncer genes 1 and 2) are the best-known genes linked to breast cancer. People who have a BRCA1 or BRCA2 mutation have a greatly increased risk of breast cancer and (for women) ovarian cancer. However, there are some options for lowering these increased risks.

Who should consider testing?

Although genetic testing for BRCA1 and BRCA2 is widely advertised, testing is only recommended for certain people, including those with:

  • A known BRCA1/2 gene mutation in the family
  • A personal history of breast cancer at age 45 or younger
  • A personal history of breast cancer at age 50 or younger and a family member (parent, sibling, child,
  • grandparent, grandchild, uncle, aunt, nephew, niece or first cousin) diagnosed with breast cancer at any age
  • A personal history of triple negative breast cancer (breast cancer that is estrogen receptor-negative,
  • progesterone receptor-negative and HER2/neu receptor-negative) diagnosed at age 60 or younger
  • A personal history of ovarian cancer
  • A personal or family history of male breast cancer
  • Ashkenazi Jewish heritage and a personal or family history of breast or ovarian cancer
  • A family member (parent, sibling, child, grandparent, grandchild, uncle, aunt, nephew, niece or first cousin) diagnosed with breast cancer at age 50 or younger
  • A family member (parent, sibling, child, grandparent, grandchild, uncle, aunt, nephew, niece or first cousin) diagnosed with ovarian cancer at any age

There is only a very small chance that your family carries a BRCA1/2 mutation if:

  • You or an immediate family member is the only person in your family with breast cancer
  • The breast cancers in your family all occurred at older ages
  • In most cases, genetic testing is not recommended when there is a low chance of finding a mutation. Remember, most breast cancers are not due to a BRCA1/2 mutation.

Weighing the risks and benefits of BRCA1/2 testing

Although testing for a BRCA1/2 gene mutation just requires a blood test, the risks and benefits should be considered before testing.

There are potential physical, emotional and financial impacts of knowing your genetic status. Thus, testing for a BRCA1/2 mutation is recommended only for people who fall into one of the categories listed above.

A health care provider or genetic counselor can talk with you about genetic testing issues (more on these issues). For more information on genetic counseling, visit the National Cancer Institute’s website (or call its hotline at 1-800-4-CANCER FREE) or the National Society of Genetic Counselors’ website.

Talking with your health care provider about your risk of a BRCA1/2 mutation

If you have concerns about your risk of having a BRCA1/2 gene mutation, talk with your health care provider. He/she can help you understand your risk and can refer you to a genetic counselor.

There are a few online tools to help you talk with your provider about your risk of a BRCA1/2 mutation and your risk of breast cancer.

Please keep in mind these tools cannot tell you whether or not you have a BRCA1/2 mutation or if you will get breast cancer. Rather, they may help you talk with your provider or a genetic counselor about these risks.

The Centers for Disease Control and Prevention (CDC) along with breast cancer advocacy organizations (including Susan G. Komen) created an online tool called Know: BRCA.

This tool can help younger women assess their risk of a BRCA1/2 mutation. This information can help you talk with your provider or a genetic counselor about your risk of a BRCA1/2 mutation.

The Office of the Surgeon General and the National Human Genome Research Institute (part of the National Institutes of Health) created an online tool called “My Family Health Portrait” to help you create a chart of your family’s health history.

This chart may be useful in discussions with your provider or genetic counselor about your family history of breast cancer and/or other health conditions.

Testing for BRCA1/2 mutations

In most cases, testing is first done on the person with breast or ovarian cancer. If no mutation is found, the cancer was probably not due to a BRCA1/2 mutation and there is no need to test other family members. If a BRCA1/2 mutation is found, other family members can be tested for the specific mutation. It is not likely that all family members will have the mutation.

For example, if your mother has a BRCA1 or BRCA2 mutation, there is only a 50 percent chance that you will also have a mutation (you get half of your genes from your mother and half from your father).

If your family members with breast cancer or ovarian cancer are deceased or are not willing to be tested (or if your family medical history is unknown), a genetic counselor can help you decide whether it would be useful for you to have BRCA1/2 testing.

Testing for other gene mutations

Of the genes linked with breast cancer, BRCA1 and BRCA2 are the most well-understood. When a person is found to have a mutation in one of these genes, there are special recommendations for breast cancer screening, risk-lowering options and care.

So, genetic testing for BRCA1/2 mutations can affect a person’s medical care.

Inherited gene mutations in some other genes such as p53, CHEK2, ATM and PALB2, also increase breast cancer risk. Testing for some of these mutations exists.

However, these gene mutations are rare and little is known about how to tailor medical care to people with these mutations. So, although testing for multiple gene mutations is becoming more available, health care providers do not yet know how to use much of the information from these tests.

If your family members with breast cancer or ovarian cancer are deceased or are not willing to be tested (or if your family medical history is unknown), a genetic counselor can help you decide whether it would be useful for you to have testing for other inherited gene mutations.

At-home genetic testing

You may have seen ads for at-home genetic testing kits. These kits are not recommended for assessing breast cancer risk. The U.S. Food and Drug Administration, U.S. Federal Trade Commission and Centers for Disease Control and

Prevention all caution against the use of at-home testing kits. The results of any genetic test should be interpreted by a trained health care provider or genetic counselor [261-263].

BRCA1/2 genetic test results

Results from a BRCA1/2 test show whether there is a mutation related to cancer in either the BRCA1 or BRCA2 gene. There are three possible results:

  • No mutation (negative or normal)
  • A mutation linked to cancer (positive or carrier)
  • A mutation not currently known to increase breast cancer risk (called a variant of uncertain significance)
  • Having a BRCA1/2 mutation does not mean you will get breast cancer. Some people with a mutation will never get breast cancer. And, people without a mutation are still at risk. Most women who develop breast cancer do not have a BRCA1/2 mutation.

If you have a BRCA1/2 mutation, there are some options to help lower your risk of breast cancer. You should discuss these options with your health care provider.

No matter whether or not you have a BRCA1/2 mutation, there are things you can do that may lower your breast cancer risk.

Benefits of BRCA1/2 genetic testing

Emotional benefits

For some people, learning their genetic test results (even if a BRCA1/2 mutation is found) brings a sense of relief and empowerment. Some may even find that learning they have a BRCA1/2 mutation is less stressful than wondering whether they have one.

BRCA1/2 carriers are often hopeful that they will benefit from the risk-lowering options available today.

Testing negative for a BRCA1/2 mutation can bring a sense of relief about the risk of breast and ovarian cancer for you and for your children.

Options for BRCA1/2 carriers to lower their risk of breast cancer

  • Taking a risk-lowering drug (tamoxifen or raloxifene)
  • Having a prophylactic mastectomy
  • Having a prophylactic oophorectomy

If you are a BRCA1/2 carrier, talk to your health care provider about the pros and cons of these options. Take the time to make decisions that are right for you—don’t feel you need to rush.

Learn more about options for women at high risk.

Breast cancer screening for BRCA1/2 carriers

Knowing you have a BRCA1/2 mutation allows you to personalize your breast cancer screening plan. There are special screening guidelines for people with a BRCA1/2 mutation.

For example, women with a BRCA1/2 mutation are screened more often and start screening at a younger age than other women. Screening with breast MRI in combination with mammography is also recommended for women who have a BRCA1/2 mutation.

Mammography plus breast MRI is better than mammography alone at finding breast cancer in women with a BRCA1/2 mutation [95].

No matter the test result, it is important to follow breast cancer screening guidelines.

Learn more about breast cancer screening for women with a BRCA1/2 mutation and other women at higher risk.

Learn about breast cancer screening for women at average risk.

Learn about breast cancer screening for men at higher risk due to a BRCA1/2 mutation or a strong family history.

Screening and risk-lowering options for ovarian cancer

Women who have a BRCA1/2 mutation also have a higher risk of ovarian cancer. These women may consider prevention options (such as prophylactic oophorectomy) to reduce the risk of ovarian cancer.

At this time, screening methods to detect early stage ovarian cancer are still under study.

Learn more about risk-lowering options for women at higher risk.

Benefits for family members

Getting genetic testing lets you share your test results with family members who may benefit from having the option of genetic testing. Remember, just because one family member has a BRCA1/2 mutation does not mean that everyone in the family has the mutation.

Source & More Info: Susan G. Komen and Cancer Research UK

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