BRCA genes and inherited breast and ovarian cancer – diagnostic

This leaflet has been written for people who have a personal or family history of breast or ovarian cancer that could be explained by an inherited factor, and who are considering having genetic testing. It has been written for use with a clinical genetics appointment and may answer some of your questions.

Is breast and ovarian cancer inherited?

It is rare for breast and ovarian cancer to be caused by a high risk gene. However, breast cancer occurs in many women, with around one in every eight in the UK developing the disease during their lifetime. Ovarian cancer develops in around one in 50 women in their lifetime. In about five to 10 per cent of these cases, a specific gene alteration (mutation) plays a part. We know of two genes, called BRCA1 and BRCA2. If they are altered, that person has a substantially increased chance of developing breast, ovarian or prostate cancer.

What are BRCA1 and BRCA2 genes?

Our genes can be found in almost every cell in our body. They are the instructions that enable our bodies to grow and function correctly. BRCA1 and BRCA2 are tumour suppressor genes that help to protect us from developing cancer. An alteration can affect the function of the gene. This can increase the chance of developing breast, ovarian or prostate cancer, which is more likely to occur at a younger age.

How are the BRCA1 and BRCA2 genes inherited?

All our genes come in pairs; we inherit one of the pair from our mother and the other from our father. When we have children, we randomly pass on one of each pair. If a person has an alteration in a BRCA1 or BRCA2 gene, each of their children (male or female) has a 50:50 or one in two chance of inheriting it. An alteration can be inherited from either parent.

If a person has not inherited a BRCA1 or BRCA2 alteration, they cannot pass it on to their children.

Can I have a test to see if the cancers in my family are due to an alteration in either BRCA1 or BRCA2?

Possibly. A person’s genes can be examined from a blood sample. At present, however, it is usually only offered to families with a strong history of breast, ovarian or prostate cancer. This is because only a small number of people with these cancers will have a BRCA1 or 2 gene alteration and because the test results can be difficult to interpret. Under current guidelines there needs to be at least a 10% chance of finding a BRCA1 or 2 gene alteration for testing to be offered.

How can I/my family go about testing?

Ideally, we would start by obtaining a blood sample from a family member who has had breast, ovarian or prostate cancer. The sample is sent to Bristol Genetics Laboratory (BGL) and they check the BRCA1 and 2 genes to see if any alterations are present. There can be many different alterations in the BRCA1 or 2 genes, for example there may be a large section of the gene missing or a single letter changed in the gene code. This type of test is known as a diagnostic test.

If a gene alteration is found, family members can be tested for this specific alteration to see if they have an increased risk of developing breast and ovarian or prostate cancer. This type of test is known as a predictive test.

We know at present we cannot find all the causes of inherited breast cancer. Our techniques are constantly improving, and in years to come, testing will be more straightforward. At the moment, some families are likely to have a gene alteration, but our tests are not able to find it.

Can I get an uncertain result?

Sometimes we find an alteration in the genetic code where we are not sure of its importance. This is called a variant of uncertain significance (VUS). If we are uncertain whether the gene alteration found is the cause of the cancers in your family, we will not be able to offer relatives a genetic test that helps predict the chances of developing a cancer. We may, however, ask for extra samples from you or other family members to try to gather more information. Often these extra tests help to decide that the VUS is not the explanation for your family history of cancer.

What if a relative with breast, ovarian or prostate cancer is not available for testing? Can I be tested even if I have never had cancer?

In some cases, where there is no affected family member available for testing we may:

Offer testing to someone in the family who has not had a cancer. This may be offered if the family history gives a high enough chance that there is a BRCA1 or 2 gene alteration. (The relative without cancer must have a 10% chance of having a gene alteration). Testing someone who has not had cancer may make some results harder to interpret. For example, if no gene alteration is found we would not know whether there is a BRCA1 or 2 gene alteration that this relative has not inherited or there is another cause for the family history.
It may be possible to test a tumour sample from an affected relative who has passed away. Testing tumour samples is more technically difficult than testing a blood sample. It is possible that this test will not work because of the way the tumour samples are stored.

Does everyone who has an alteration in BRCA1 or 2 develop cancer?

No. The chance of developing these cancers is not 100 percent. We do not yet know why some people with the alteration develop cancer and some do not. Lifestyle or other genetic factors are likely to play a role. It is important to note that developing cancer is not the same as dying from cancer. Even if cancer develops, there is often a chance that the disease can be cured if it is found and treated early.

What are the cancer risks associated with alterations in BRCA1 and BRCA2?

The figures below outline the increased risks of cancer over a lifetime for a person who has a BRCA1 gene alteration.

Breast cancer

Female carriers - 60% to 80%
Male carriers - 1%
Members of the general population - 12% (female), 0.5% (male)

Ovarian cancer

Female carriers - 40% to 60%
Male carriers - not applicable
Members of the general population - 1% to 2% (female)

Prostate cancer

Female carriers - not applicable
Male carriers - minimal increased risk
Members of the general population - 12%

Pancreatic cancer

Female carriers - up to 3%
Male carriers - up to 3%
Members of the general population - 1.5%

or a person who has a BRCA2 gene alteration:

Breast cancer

Female carriers - 60% to 80%
Male carriers - 6%
Members of the general population - 12% (female), 0.5% (male)

Ovarian cancer

Female carriers - 10% to 30%
Male carriers - not applicable
Members of the general population - 1% to 2% (female)

Prostate cancer

Female carriers - not applicable
Male carriers - 25% (often more aggressive in younger men)
Members of the general population - 12%

Pancreatic cancer

Female carriers - 2% to 7%
Male carriers - 2% to 7%
Members of the general population - 1.5%

Remember, 10 per cent means one person in every 10 will develop this cancer in their lifetime.

For someone who has already had cancer once, there is also an increased chance of developing a completely new cancer. This is different to cancer that reoccurs or spreads from a first (original) cancer. Please discuss this with your clinician.

Are BRCA1 or 2 the only genes that can cause inherited breast cancer?

No. There are other genes that increase the chance of developing breast and/or ovarian cancer. There is a panel of breast cancer genes that can be tested if there is a strong enough family history of breast cancer or a panel of ovarian cancer genes if there is a strong enough family history of ovarian cancer. The threshold for panel testing is higher than that for testing the BRCA1 and 2 genes only. Research is continually updating our knowledge in this area. For more information about these gene panels ask your clinician.

What are the implications of BRCA1 and 2 testing?

If an alteration is found that increases the chance of developing cancer, some people may worry that genetic testing will affect their insurance prospects (for example, health, life, or disability insurance). Currently, the insurance industry has agreed it will not ask about genetic testing for the majority of policies, but this position may change in the future.

Some people go through a range of emotions when they are told they have a gene alteration that increases their chance of developing cancer. They may feel angry, shocked, anxious or guilty about possibly passing the gene alteration on to children. Some people may also feel guilty if they do not have a familial gene alteration when other close family members do.

Genetic testing in a family can affect other family members, who may need to be told that they too are at a higher risk. Different family members may have different reactions to this information. Therefore, genetic testing may affect relationships within families. Your clinician will provide you with a letter that you can pass on to relatives to help them access genetic testing.

Can having a BRCA1 or 2 gene alteration affect cancer treatment?

There are new drugs available called PARP inhibitors (Olaparib and Niraparib) which have been shown to improve survival in individuals diagnosed with breast and ovarian cancer who have a BRCA1 or 2 gene alteration.

What screening is available for women with a BRCA1 or 2 gene alteration?

MRI (magnetic resonance imaging)

Breast MRI is the most effective form of breast screening for younger women. Breast MRI is offered to women with a BRCA1 or 2 gene alteration every year from 30 until 49 years of age. Women who have a 50% or 1 in 2 chance of having a BRCA1 or 2 gene alteration are also eligible for this screening.

Mammography

This form of screening has not been proven to be effective in women under the age of 40. It has been shown to be beneficial over the age of 40, especially alongside breast MRI.

Women with a BRCA1 or 2 gene alteration are offered annual mammograms from 40 until 69 years of age. This screening is also offered to women who have a 50% or 1 in 2 chance that 10 BRCA genes and inherited breast and ovarian cancer they have a BRCA1 or 2 gene alteration. From 70 years of age, women can request to have a mammogram every three years by contacting their local breast unit directly.

Is there any screening for ovarian cancer?

Some recent evidence suggests that ovarian screening may help to detect ovarian cancer at an earlier stage. However, there is not enough evidence yet that this screening saves lives. Therefore, it is not currently offered as part of NHS treatment.

Ovarian screening is available privately. Your genetic counsellor or clinical genetics doctor should be able to provide you with more information about this if you are interested.

Screening involves a combination of an ultrasound scan and a blood test to look at CA125 levels (CA125 is a marker in the blood which can be increased in someone with ovarian cancer).

Is there any other recommended screening?

If you have a family history of pancreatic cancer, you could talk to your clinician about whether or not pancreatic screening is an option for you.

BRCA1 and 2 gene alterations may be associated with increased risks of developing other types of cancer. The risks of these are likely to be small and there is no additional screening recommended currently.

Risk reducing breast surgery (risk reducing bilateral mastectomy)

This is the surgical removal of healthy breasts to prevent a cancer developing. This has been shown to reduce the chance of developing breast cancer by 90 to 99 per cent. It does not remove all the risk, as the surgery cannot remove every breast cell. It is a major operation that can have serious complications, so it requires careful consideration.

Risk reducing removal of the ovaries and fallopian tubes (risk reducing bilateral salpingo-oophorectomy)

This is the surgical removal of healthy ovaries and fallopian tubes to prevent cancer developing. Having the ovaries removed reduces the risk of ovarian cancer by 95 percent. There is still a small chance of an ovarian-like cancer developing in the surrounding tissue that is left. This is estimated to be between two to five per cent in a lifetime. In some circumstances, this surgery may also help to reduce the chance of developing breast cancer if carried out before the natural menopause. Having ovaries removed will start an immediate menopause. Therefore, it may be appropriate to have some form of hormone replacement therapy (HRT) until 50 years of age. HRT may not be recommended for women who have had hormone receptor positive breast cancer.

Is there any medication which can reduce the risk of developing breast and ovarian cancer?

Taking certain medications for five years has been shown to reduce the risk of breast cancer in women at increased risk. Tamoxifen can be offered prior to the menopause or Tamoxifen, Raloxifene and Anastrazole after the menopause. These drugs are associated with side effects. Please ask your clinician about this if you are interested and/or see our separate chemoprevention leaflet.

Symptom awareness

We also recommend breast and ovarian cancer awareness for women and prostate and breast awareness for men. Your clinician will provide you with the relevant booklets from Macmillan with more information about this. Alternatively, there is more information online at www.macmillan.org.uk.

These booklets also include information about lifestyle factors which can help to reduce cancer risk in general.

Is there any screening for men with a BRCA1 or 2 gene alteration?

There is currently no national screening programme for prostate cancer in the UK. This is because it has not been proven that the benefits outweigh the risks. Instead of a national screening programme, there is an informed choice programme, called prostate cancer risk management. The PSA test is a blood test to help detect prostate cancer. It measures the level of prostate-specific antigen (PSA) in your blood. This is available to healthy men aged 50 or over, who ask their GP about PSA testing. It aims to give men good information about the pros and cons of a PSA test.

BRCA2

Given the increased risk, men with a BRCA2 alteration can be referred to a urologist to discuss the option of prostate screening in more detail. Currently, prostate screening involves measuring PSA levels but may also involve an initial MRI.

BRCA1

The risk of developing prostate cancer is not greatly increased. Therefore, prostate screening is not currently offered to men with a BRCA1 gene alteration, although they could discuss with their GP about prostate cancer risk management.

Are there any options for people with a BRCA1 or 2 alteration who are planning a family?

Many people with a BRCA1 or 2 gene alteration opt to have children in the usual way. Alternatively, women or men with a BRCA1 or 2 gene alteration may have the option of having pre-implantation genetic diagnosis (PGD). PGD involves undergoing the fertility treatment in vitro fertilisation (IVF).

PGD has the extra step of genetic testing of the embryos (fertilised eggs). The aim is to only put embryos back into the womb which have not inherited the gene alteration. The genetic counsellor or clinical genetics doctor can discuss this in more detail with individuals who are keen to consider this option. Testing in pregnancy is theoretically possible, but not often considered for conditions that affect people as adults.

Is there an alternative to genetic testing?

You may decide not to have genetic testing. Whether or not you are tested, you should talk to your clinician about screening options for you and your relatives.

I’ve heard of research studies involving people with a family history of cancer. How can I find out more?

There may be research studies that you could take part in if you wish. It is important to remember that research studies may not benefit you directly, but may help future generations.

Talk to your clinician about all of these topics before deciding on a plan of action that is best for you.

If you or the individual you are caring for need support reading this leaflet please ask a member of staff for advice.

How to contact us:

Brunel building
Southmead Hospital
Westbury-on-trym
Bristol
BS10 5NB