Everything you need to know about hereditary breast and ovarian cancer

Genes and mutations

We all have thousands of genes that provide the instructions for our bodies to function optimally.

All cancers begin when changes occur in our genes. A change in a gene that disrupts its function is called a ‘mutation’, a “gene fault” or a ‘pathogenic variant’. Cancer usually results from an accumulation of many mutations. Most of the time, those mutations are confined (at least initially) to genes in the cells of the organ or tissue where they started. We call these type of genetic mutations ‘somatic’. Somatic mutations are not inherited from our parents, and they are not passed down to our children. This is why the majority of cancers do not ‘run in families’.

A small number of people are born with a gene fault or mutation that increases their chance of developing certain types of cancer.

In these people, cancer can get a ‘head start’ because when the first mutation is inherited from a parent it is present in every cell of a person’s body. This does not mean that a person will develop cancer in every cell of their body. In fact, we know that even when people are born with these gene faults or mutations, it is not guaranteed that they will develop cancer, but they are at a higher chance of developing certain types of cancer, depending on which specific gene is involved.

Understanding hereditary breast and ovarian cancer

In the mid 1990’s, scientists discovered the first two genes in which inherited mutations can increase a person’s chance of developing breast and ovarian cancer. They were named BRCA1 and BRCA2 for BReast CAncer genes 1 and 2. All people, both male and female, have two copies of both BRCA1 and BRCA2, one inherited from their mother and one inherited from their father. BRCA1 and BRCA2 belong to a family of genes called tumour suppressor genes, and their normal job is to protect us from developing cancer. It is only when a mutation occurs that disables one of these genes that a person becomes predisposed to cancer. BRCA1 and BRCA2 are what is known as “high penetrance” genes. That means that a mutation in these genes causes a high risk of cancer in the person who carries it.

A woman who carries a mutation in one of her two copies of BRCA1 or BRCA2 has approximately a 70% chance of developing breast cancer over a normal lifespan. She also has a 44% lifetime risk (BRCA1 mutations1) or a 17% lifetime risk (BRCA2 mutations2) of developing ovarian cancer.

Carriers of BRCA2 mutations also have an increased risk of developing pancreatic cancer, and, for males, prostate cancer and male breast cancer.

BRCA1 and BRCA2 were the first genes discovered to be involved in hereditary breast and ovarian cancer, and for more than a decade they were the only ones we knew about. However, in the last decade many more genes have been discovered, mutations in which also predispose women to either breast cancer, to ovarian cancer, or to both. Some also cause other types of cancer.

However, most of the more recently discovered genes have a lower ‘penetrance’ than BRCA1 or BRCA2, meaning that they confer a smaller lifetime risk of developing cancer than the 70% we see in BRCA1 and BRCA2. It is likely that more genes which can predispose to breast or ovarian cancer will be discovered in coming years.

I have had breast cancer – could it be hereditary?

Breast cancer is one of the most common cancers affecting women, affecting approximately 1 in 7 of Australian women3. Inherited mutations in the BRCA1 and BRCA2 genes are rare – found in only around 1/225 – 1/500 (0.2% – 0.4%) of people4, and mutations in many of the other breast cancer genes are even rarer.

So, the majority of people who are diagnosed with breast cancer will not have an inherited gene fault predisposing to breast cancer.

A person who has inherited a mutation in a breast cancer predisposing gene will often (but not always) have some of the following features in themselves or in their family history:

Individuals who have been diagnosed with breast cancer at a young age (under 50-years-old)
More than two relatives on the same side of the family who have also been diagnosed with breast cancer
Relatives who have had ovarian cancer, prostate cancer or pancreatic cancer, especially if they were young at the time of diagnosis
Males relatives who have had breast cancer
Ashkenazi Jewish ancestry (Jewish ancestors who came from central or Eastern Europe)

Sometimes, even in the absence of any of these features, a woman whose breast cancer has specific features (such as ‘grade 3 triple negative’ breast cancer, which has no receptors for oestrogen, progesterone and does not over-express the HER2 protein) may be at increased risk of having a hereditary predisposition to breast cancer.

If you have been diagnosed with breast cancer, ask your doctor whether they feel that genetic testing would be indicated for you. It will be helpful if you can collect information about your family history of cancer prior to having this discussion.

Your doctor may organise genetic testing for you directly, or they may refer you to a genetic counsellor/genetics clinic or familial cancer service to have this done.

I have had ovarian cancer – could it be hereditary?

Ovarian cancer is less common than breast cancer, affecting just under 1% of Australian women. There are several different types of ovarian cancer and some of them (such as cancers arising from egg cells) are rarely hereditary. But for other types of ovarian cancer, more than 10% can be caused by hereditary gene mutations.

A person who has inherited a mutation in an ovarian cancer predisposing gene will often (but not always) have some of the following features in themselves or in their family history:

Individuals who have been diagnosed with ovarian cancer at a young age (under 50-years-old)
More than two relatives on the same side of the family who have also suffered from breast or ovarian cancer, especially if any were diagnosed under 50 years of age
Relatives who have had prostate cancer or pancreatic cancer
Males relatives who have had breast cancer
Ashkenazi Jewish ancestry (Jewish ancestors who came from central or Eastern Europe)
A personal or family history of bowel or uterine cancer

Sometimes, even in the absence of any of these features, a woman whose cancer has specific features (a high grade serous ovarian cancer, or a cancer arising in the fallopian tube or the peritoneum) may be at increased risk of having a hereditary predisposition to ovarian cancer. Sometimes genetic testing is performed on the DNA from ovarian tumours by oncologists, to help determine which drugs would work best to treat the tumour. If this genetic testing finds a mutation in an ovarian cancer predisposing gene, such as BRCA1 or BRCA2, follow up genetic testing on DNA from a blood sample is recommended to find out if the mutation that was found in the tumour is somatic (i.e. has arisen in and is confined to the tumour) or if it is inherited.

Sometimes a special protein-staining test is performed on ovarian tumours. If this special test reveals that certain proteins are missing in the tumour, follow up genetic testing on DNA from a blood sample is recommended to find out if the person might have Lynch syndrome (an inherited predisposition to bowel, uterine and ovarian cancer). If you have been diagnosed with ovarian cancer, ask your doctor whether they feel that genetic testing would be indicated for you. It will be helpful if you can collect information about your family history of cancer prior to having this discussion. Your doctor may organise genetic testing for you directly, or they may refer you to a genetic counsellor/genetics clinic or familial cancer service to have this done.

What does genetic testing involve?

Genetic testing can be done using DNA extracted from white blood cells (a blood test) or from cells present in saliva. Unlike regular blood tests, it usually takes around four to six weeks (instead of days) to get a result.

Frequently asked questions

What happens if testing shows that my cancer is hereditary?
If your genetic test result shows that you have inherited a gene fault in a cancer-predisposition gene, you will usually meet with a genetic counsellor or a with a doctor who specialises in genetic conditions, if you haven’t done so prior to testing. the genetic counsellor or a doctor specialising in genetic conditions to discuss:
The cancer risks that are associated with the gene fault you have
The different options you have to manage your cancer risks, which may include:
Tailored screening programs for the cancers that you are at risk of, such as annual breast MRIs or annual mammograms for women at increased risk of developing breast cancer
Risk-reducing medications such as tamoxifen that can be taken to lower the risk of developing breast cancer for certain gene mutations
Preventative surgery. Some women at increased risk of developing breast cancer will prefer to have a preventative mastectomy (with or without breast reconstruction) rather than having ongoing screening. For women at increased risk of ovarian cancer, preventative surgery to remove the ovaries is generally recommended from around age 40 due to the lack of any effective screening tests for ovarian cancer
The implications for your relatives, such as siblings, children and the wider family
Depending on the particular genetic mutation found, there may be additional drugs such as PARP inhibitors, which your oncologist can use to treat your cancer
What I if already know that the breast and/or ovarian cancer in my family is hereditary?
If a relative has already undergone genetic testing and has been found to carry a mutation in a cancer-predisposing gene, then you are eligible to have ‘predictive’ genetic testing to see if you have also inherited the same gene mutation present in your relative. For most genes, predictive testing is funded by Medicare. If you are in this situation ask your GP to refer you to a genetic counsellor, genetics clinic or familial cancer service. Some services do not require a GP referral for predictive testing.
What if I have not had cancer, but am worried about my family history of cancer?
Genetic testing is most informative if it is performed in the first instance in a person who has had a cancer. However, sometimes this is not possible; for example, if family members have lost contact, if there are no cancer survivors in the family or if those who have survived do not wish to undergo genetic testing. In this circumstance, genetic testing is generally not offered through the public hospital system (genetics clinics/familial cancer services), but can be accessed for those who wish to self-fund genetic testing through private genetic counselling clinics or services.
Will genetic testing affect my health insurance or life insurance?
Some people worry about whether having genetic testing might affect their health or life insurance, or their relatives ability to get these types of insurance. In Australia, genetic testing will NOT affect access to private health insurance for you or any of your relatives. However other insurance products such as life insurance, death, disability, trauma and income protection insurance are based on your health information. When applying for a policy, you must provide information about any cancers that have been diagnosed in you or your first degree relatives. Previously, providers of these types of insurance products were able to request information about genetic testing results, however, a moratorium on Genetic Tests in Life Insurance came into effect from 1 July 2019 preventing the use of genetic test results for the assessment of insurance applications up to the value of $500 000 (for death and total permanent disability), $200 000 for trauma and $4 000 a month for income protection. This moratorium was initially planned for 5 years (until 2024), but has now been extended indefinitely.

References

- Facts for people and families with a faulty BRCA1 gene. eviQ. Retrieved 14 April 2023 3426-Facts for people and families with a faulty BRCA1 gene | eviQ
- Facts for people and families with a faulty BRCA2 gene. eviQ. Retrieved 14 April 2023 3427-Facts for people and families with a faulty BRCA2 gene | eviQ
- Australian Government. (2022). Cancer Australia, Cancer types. Retrieved on 30 March 2023 from https://www.canceraustralia.gov.au/affected-cancer/cancer-types/breast-cancer/breast-cancer-australia-statistics
- Cancer predisposition genes: population carrier frequency. eviQ. Retrieved 14 April 2023 3750-Cancer predisposition genes: population carrier frequency | eviQ
- Life Insurance Products and Genetic Testing in Australia. Centre for Genetics Education. Retrieved 14 April 2023 Life_Insurance_fact_sheet-CGE.pdf (genetics.edu.au)

The content on the Icon Oncology website is for informational purposes only and should not be considered medical advice. It is not a substitute for consultation with a qualified medical practitioner. For personalised medical guidance, please consult with your GP or another qualified healthcare provider.