Genetic mutations that increase breast cancer risk

Around 5 to 10% of breast cancers are thought to be inherited or ‘hereditary’. This means a gene mutation or abnormality passes from a mother or father to their child and leads to the development of breast cancer. Most breast cancers are not inherited.

You may be concerned about your risk if a close family member – your mother, father, sister or daughter – has been diagnosed with breast cancer.

We explain the different genes that may be related to breast cancer developing.

The connection between genes and breast cancer

Each human cell has about 25,000 genes. Our genes carry information that sets the features or characteristics we inherit from our parents. The variation in our genes is what makes us unique, in our family and within our ethnicity.

If a variation alters the way the gene works, the changes are called gene mutations or pathogenic variants.

We can inherit genetic changes from our parents that increase our cancer risk.

Cancer begins when genes in cells become abnormal and the cells starts to grow and divide in an uncontrolled manner. In hereditary breast cancer, changes are often in genes that normally work to stop abnormal cell growth.

It is important to remember genetic mutations are uncommon.

To estimate the risk more accurately, consult the familial genetics team at a family cancer centre. 

BRCA1 and BRCA2 genetic mutations

BRCA1 and BRCA2 are the most common inherited gene mutations that increase the risk of breast cancer. BRCA stands for BReast CAncer.

Abnormalities in BRCA1 or BRCA2 occur in about 1 in 400 Australians (0.2%). They are more common in some ethnic groups – for example in about 1 in 40 people (2.5%) with Ashkenazi Jewish heritage.

BRCA1 and BRCA2 genes usually protect us from developing breast cancer. When you inherit a mutation in one of these genes, your risk of developing cancer is higher.

For women with a BRCA1 or BRCA2 mutation, the risk of being diagnosed with breast cancer during their lifetime is up to 72%.

Men with a BRCA2 mutation can have a higher risk of breast cancer than men who do not. This risk is about 8% by the time they are 80 years old.

Triple negative breast cancer is more common in women with a BRCA1 mutation.

Men and women can inherit, carry and pass on a gene mutation that increases the risk of breast cancer.

If one family member has a genetic mutation linked to breast cancer it does not mean that all family members will have it.

Other cancers related to these genes include ovarian cancer, pancreatic cancer, and prostate cancer in men.

PALB2 gene mutation

PALB2 is a high-risk mutation. It’s the third most common high-risk breast cancer gene, after BRCA1 and BRCA2.

PALB2 stands for ‘Partner and Localizer of BRCA2’. This means it works with the BRCA2 gene to repair damage and help prevent breast cancer. A mutation in the PALB2 gene increases the risk that breast cancer will develop.

An estimated 53% per cent of women with a mutated PALB2 gene will develop breast cancer by the age of 80.

A PALB2 gene mutation is also linked to an increased risk for:

triple negative breast cancer in younger women

• male breast cancer
• ovarian cancer in women
• pancreatic cancer in some families.

TP53 gene mutation

TP53 is a high-risk mutation. It is extremely rare. The TP53 gene tells the body how to make a protein that stops tumour growth.

Inheriting a faulty TP53 gene causes Li-Fraumeni syndrome. People with this disorder develop soft-tissue cancers at a young age. Women with Li-Fraumeni syndrome are more likely to develop breast cancer at a younger age and it is more likely to be HER2-positive.

This gene abnormality causes a higher risk of many types of cancer including cancers in children.

CDH1 gene mutation

CDH1 (CaDHerin 1) is a high-risk mutation. The CDH1 gene makes a protein that helps cells connect to form tissues in the body.

Women with an abnormal CDH1 gene have a higher risk of invasive lobular breast cancer. The risk is approximately 40% during a lifetime. Lobular breast cancer is the second most common type of breast cancer. Most breast cancers are ductal breast cancer. CDH1 does not increase the risk for ductal breast cancer.

PTEN gene mutation

PTEN is a high-risk mutation. The gene helps regulate cell growth by controlling how fast cells divide. It also causes damaged cells to self-destruct before they become cancerous.

An abnormal PTEN gene causes Cowden syndrome. People with this rare condition have a higher risk of:

• both non-cancerous (benign) breast tumours
• cancerous breast tumours
• cancer in the bowel, thyroid, uterus and ovaries.

The risk of breast cancer is unclear but at least moderately increased.

STK11 gene mutation

STK11 is a high-risk mutation. The STK11 (Serine/Threonine Kinase 11) gene helps control cell growth. Mutations cause non-cancerous growths/polyps in the gastrointestinal tract (Peutz-Jeghers syndrome - PJS). This is an extremely rare condition.

An abnormal STK11 gene is associated with:

• a moderately increased risk of breast cancer
• gastrointestinal cancers.

The risk of breast cancer may be lower if an individual has the genetic change but no other clinical signs of PJS.

CHEK2 gene mutation

CHEK 2 is a moderate-risk mutation. The CHEK 2 (Checkpoint Kinase 2) gene tells the body how to make a protein to stop cancer growth.

In men, abnormal CHEK2 makes male breast cancer 10 times more likely to develop. In some families the risk can be low to moderate, but moderate to high in others.

CHEK2 mutation is also associated with an increased risk for DCIS. The risks for DCIS and breast cancer are between 17% and 30%. The Breast Cancer Trials podcast What Is The CHEK2 Gene Mutation? has more information.

ATM gene mutation

ATM is a moderate-risk mutation. The ATM gene helps repair damaged DNA. An abnormal ATM gene stops the cells from repairing the damage.

In some families, inheriting an abnormal ATM gene has been linked to an increase in:

• breast cancer
• DCIS
• pancreatic cancer.

Breast cancer risk can vary from low to moderate depending on your family history.

RAD51C gene mutation

RAD51C is a moderate-risk mutation. This gene interacts with the BRCA genes. A RAD51C abnormality leads to a risk that is about double the general population risk.

This gene abnormality is more commonly linked to:

• triple negative breast cancer
• an increased risk for ovarian cancer.

NF1 gene mutation

NF1 is a moderate-risk mutation. This mutation causes a condition called neurofibromatosis type 1, which increases the risk of cancers in the central nervous system. This is an extremely rare condition.

Women with an NF1 mutation have about an 18% lifetime risk of developing breast cancer.

Mutations with an uncertain breast cancer risk

Some other gene mutations may or may increase the risk of breast cancer:

• BARD1
• BRIP1
• MLH1, MSH2, MSH6, PMS2, EPCAM (Lynch Syndrome)
• RAD51D.

These genes are involved in repairing damage to DNA. They are already linked to an increased risk for ovarian, bowel or endometrial cancer.

Some studies suggest mutations in these genes can also increase the risk of breast cancer. More research is needed.