What Are Genetic Breast Cancer Mutations?

Medically Reviewed by Sabrina Felson, MD on September 20, 2022
Written by Julie Marks
10 min read

If you have breast cancer, chances are it’s not caused by a faulty gene you were born with. Most of the time, genes that lead to the disease mutate sometime during your life and aren’t an inherited problem.

But in about 5% to 10% of cases, the cause is hereditary. This means that the cancer is due to a gene change, called a “mutation,” that’s passed down from a parent.

Researchers have identified hundreds of genes linked to breast cancer, but some seem to play more of a role than others.

Just because you have an inherited gene mutation doesn’t mean you’ll definitely get breast cancer. It only means you have a greater chance of it happening.

If you inherit a gene mutation for breast cancer, it means that you got it from one or both of your parents.

Many mutations, such as those found in the well-known BRCA1 and BRCA2 genes, are passed down in what’s called an autosomal dominant pattern. This means that inheriting one bad gene from one parent may lead to an increased chance of disease.

If one of your parents has an autosomal dominant gene mutation, there’s a 50% chance you’ll inherit it. This is why we see the disease in many relatives, but not all of them.

Genetic tests can tell you if you have an inherited gene mutation for breast cancer. You can have a test that looks for an individual gene abnormality or a larger panel test that examines several genes at one time. Experts usually recommend gene testing if you have breast cancer or strong risk factors, such as a family history of hereditary cancers. Talk to your doctor if you’d like to learn more about genetic testing.

At-risk families can take blood tests to look for mutations in these genes.

You may want to discuss genetic testing with your doctor if:

  • You have two or more blood relatives – mother, sister, aunt, cousin, or daughter – with premenopausal breast cancer or ovarian cancer diagnosed at any age.
  • You were diagnosed with breast cancer, especially before menopause, and have a blood relative with breast or ovarian cancer.
  • You were diagnosed with ovarian cancer and you have blood relatives who have had ovarian or breast cancer.
  • A male in your family has or had breast cancer.
  • You or a family member has been diagnosed with bilateral breast cancer (cancer in both breasts).
  • You were diagnosed with triple-negative breast cancer before the age of 60.
  • You are related to someone (male or female) who has a BRCA1 or BRCA2 mutation.
  • You are of Ashkenazi Jewish descent and have had breast or ovarian cancer or have blood relatives who have had breast or ovarian cancer.
  • You may also want to consider testing if you are a Black woman. Black women are just as likely to have hereditary breast cancer mutations as white women, but tend not to get tested as frequently, putting you at a higher risk of the cancer going undetected.

 

Counseling is required before having genetic testing for breast cancer. During this educational session, a health care provider will explain the benefits and risks of genetic testing and answer any questions you may have.

You’ll also have to sign a consent form. It’s an agreement between you and your health care provider, showing that you have discussed the tests and understand how the results might affect you and your family.

Here are some questions to consider when thinking about genetic testing:

  • Am I prepared to cope with the result? Are my family members also prepared, including my children and my spouse?
  • What are my goals for testing?
  • How would I use my test results? What will I do differently if the results are positive or negative?
  • With whom will I share my results?
  • Would a positive test result change relationships with my family?

The Health Insurance Portability and Accountability Act (HIPAA) of 1996 prevents insurance companies from denying coverage based on genetic information. This act also prevents insurance companies from using genetic information to determine that a health condition existed before application was made for insurance. In addition, many states have passed laws, or have legislation pending, addressing insurance concerns.

The genetic counselor will do a family pedigree to detect high-risk patterns. A family pedigree is a chart that shows the genetic makeup of a person's relatives. It’s used to analyze traits or diseases that are passed down through a family.

Then, you’ll have a blood test to learn whether you have a breast cancer gene. Keep in mind that the vast majority of breast cancer cases are not linked to a breast cancer gene. In addition, scientists do not know all of the genes that can cause breast cancer, so they can test you only for the known genes.

When someone with a cancer diagnosis and a family history of the disease is found to have an altered BRCA1 or BRCA2 gene, the family is said to have a "known mutation." If there’s a link between the development of breast cancer and a breast cancer gene, then all family members willing to have genetic testing are asked to give a sample of blood. For many people, knowing their test results is important because this information may help to guide health care decisions for themselves and their families.

Yes. There are several options for genetic testing that can be done on your own. Companies like Veritas Genetics and Color Genomics offer testing kits that look for BRCA1 and BRCA2. You will need a doctor’s approval to order the kits. Both companies can connect you with a health care provider to get the necessary approval and help explain the results. These tests are usually more affordable ($200-$300) than tests ordered through a hospital but can miss key mutations that could clue doctors into a possible breast cancer diagnosis.

A negative genetic test means that a breast cancer gene mutation was not identified. If other genetic testing has identified a mutation in your family, a negative test means you do not have the specific mutation. Therefore, your risk of cancer is the same as someone in the general population who has a family history of breast cancer.

If a BRCA1 or BRCA2 mutation has not been previously found in your family, a negative result should be interpreted cautiously. There is still a chance that you may have a higher risk for breast cancer because of changes in genes other than those that doctors can test for.

A positive test result means that a mutation known to raise the risk of breast and ovarian cancers was identified.

Genetic testing is not 100% accurate. If a test is negative, a person still has a chance of getting breast cancer. If the test is positive, there is still a chance of not getting breast cancer.

Genetic testing is costly, ranging from about $400 to more than $3,000, depending on the type of test. Insurance coverage varies.

The results of genetic tests won't be available for several weeks. The length of time it takes to get results depends on the tests performed and under what circumstances they are done.

Legislation has been enacted to protect people who may have a documented genetic risk of cancer from employment or insurance problems. The best thing you can do is to become involved with an established genetic registry that can counsel people who have a genetic risk for cancer.

But for some people, genetic testing may help you make informed medical and lifestyle decisions while easing the anxiety of not knowing your genetic background. You can also make a decision regarding prevention, with both medications and prophylactic surgery. In addition, many people take part in medical research that, in the long run, may lower their risk of death from breast cancer.

If your genetic testing shows you have a mutation linked to cancer, there are still several steps you can take to lower your chances for developing breast cancer.

  • Maintain a healthy weight.
  • Stay physically active. The American Cancer Society recommends you get at least 150 to 300 minutes of moderate-intensity or 75 to 150 minutes of vigorous-intensity activity each week. Moderate activity can be something like a quick-paced walk, while vigorous activity would have you breaking a sweat.
  • Limit alcohol intake.
  • Studies show decreased risks of breast cancer for women who breastfeed for several months after giving birth.
  • The American Cancer Society recommends choosing non-hormonal options to treat menopause symptoms instead of hormone therapy.

If you have an increased risk, you can also consider counseling to help navigate the emotions surrounding the test results, and speaking with a health care professional about next steps.

Researchers have identified several key gene changes linked to breast cancer. Some of these pose a high risk, while others seem to be less significant.

BRCA1 and BRCA2

The BRCA1 (breast cancer gene one) and BRCA2 (breast cancer gene two) inherited gene mutations are the most common cause of hereditary breast cancer. Mistakes in these genes account for up to 10% of all breast cancers. BRCA mutations also raise your chances for ovarian cancer, pancreatic cancer, and, in men, prostate cancer. A BRCA mutation may raise your chances of colon cancer. Women with a BRCA1 or BRCA2 mutation have up to a 72% chance of breast cancer during their lifetime.

PALB2

Normally, the PALB2 gene makes a protein that works with the BRCA2 gene protein to repair damaged DNA and stop tumor growth. But defects in the gene can lead to a higher likelihood of breast cancer. Some studies suggest that women with a PALB2 mutation have a 14% chance of breast cancer by age 50 and a 35% chance by age 70.

PIK3CA

The PIK3CA gene gives instructions to make a protein that’s important for many cell functions. A PIK3CA mutation isn’t inherited – you can’t pass it down to your children. Instead, it’s a mutation that you develop during your life, called a sporadic mutation. PIK3CA gene mutations are found in about 30% to 40% of breast cancers. It’s important to know your tumor’s PIK3CA status because it may affect how your doctor treats your cancer. Surgeons can remove tissue in your tumor (called a biopsy) to test your breast tumor for a PIK3CA mutation, or in some cases, a blood test can find the defect.

HER2

The HER2 gene makes a protein called HER2 (human epidermal growth factor receptor 2). This protein is found on the surface of all breast cells and that helps them grow. If the HER2 gene malfunctions and makes too many copies of itself, it tells cells to make too much HER2 protein. This causes the cells to grow out of control.

Like PIK3CA, HER2 is not an inherited gene mutation. Most breast cancer is HER2-negative. Research suggests about only 10% to 20% of cases are HER2-positive. This means there’s a change in the HER2 gene that makes breast cells grow and divide out of control. If you have invasive breast cancer, your doctor will probably test your tumor tissue for HER2 after you have a biopsy.

PTEN

PTEN is a gene that helps control cell growth. An inherited change in PTEN can cause Cowden syndrome, a disorder that puts you at risk for cancerous and noncancerous breast tumors and other growths. Women with a PTEN mutation have a lifetime breast cancer chance of between 25% and 50%, though some studies suggest the odds are even higher.

TP53

The TP53 gene helps stop the growth of cells that have damaged DNA. An inherited TP53 mutation causes Li-Fraumeni syndrome, a disorder that ups your chances of breast cancer, leukemia, brain tumors, and cancers called sarcomas. One study found women with Li-Fraumeni syndrome have a 54% chance of breast cancer by age 70.

ATM

The ATM gene normally helps repair damaged DNA, but some people who inherit one bad copy of the gene are at high risk for breast cancer and pancreatic cancer. Research suggests the lifetime chance of breast cancer for those who carry an ATM mutation is between 33% and 38%. Those who have a type of mutation that affects a specific location on the ATM gene have a 69% lifetime chance.

CDH1

CDH1 makes a protein that helps cells bind together to create tissue. People with a faulty CDH1 gene are more likely to develop a rare type of stomach cancer. Women with this mutation also have a 39% to 52% lifetime chance of invasive lobular breast cancer (breast cancer that starts in the lobules of the breast, the glands that make milk).

Researchers have discovered many other genes related to breast cancer.

Changes in the following genes may also raise your chances:

  • BARD1
  • CHEK2
  • NBN
  • NF1
  • STK11
  • MSH2

 

Women who inherit the mutated BRCA1 gene have a 55% to 65% risk of breast cancer by age 70. Women with mutated BRCA2 have about a 45% risk. Men with a BRCA mutation are also at a higher risk of breast cancer.

Transgender and gender expansive people (those who don’t identify as strictly male or female) can also inherit these gene mutations. If you’re part of this community, you should consider that top surgery, which removes breast tissue, doesn’t completely remove this risk.

Either mutation brings a higher risk of getting breast cancer at a younger age (before menopause).

People who have a mutated BRCA1 or BRCA2 gene have a higher risk of a second primary breast cancer, too. Bilateral breast cancer (cancer in both breasts) is also more common in women who carry a BRCA1 or BRCA2 gene.

These mutations also raise your risk of ovarian cancer, fallopian tube cancer, peritoneal cancer, and pancreatic cancer. Men face a higher risk of prostate cancer.

 

 

Show Sources

SOURCES:

Breastcancer.org: “Genetics,” “Researchers Identify 110 Genes Associated With Breast Cancer,” “Risk of Developing Breast Cancer,” “Types of Genetic Tests,” “HER2 Status.”

CDC.

Journal of Cancer Education: “What Black Women Know and Want to Know About Counseling and Testing for BRCA1/2.”

National Institutes of Health, Genetics Home Reference: “Breast Cancer,” “PIK3CA gene.”

American Cancer Society: “Breast Cancer Risk Factors You Cannot Change,” “Can I Lower My Risk of Breast Cancer?” "Genetic Testing: What You Need to Know,” “FDA Approves First P13K Inhibitors for Breast Cancer,” “Breast Cancer HER2 Status,” “Can Ovarian Cancer Be Prevented?” “American Cancer Society Recommendations for the Early Detection of Breast Cancer.”

MedlinePlus: “Autosomal dominant.”

Mayo Clinic: “Autosomal dominant inheritance pattern,” “BRCA gene test for breast and ovarian cancer risk.”

Trends in Molecular Medicine: “Cancer-Associated PIK3CA Mutations in Overgrowth Disorders.”

Moffitt Cancer Center: “What Causes HER2 Positive Breast Cancer?”

National Comprehensive Cancer Network.

National Breast Cancer Coalition.

National Breast Cancer Foundation: “BRCA: The Breast Cancer Gene.”

National Cancer Institute: “NCI Dictionary of Cancer Terms: Lobule,” “BRCA Mutations: Cancer Risk and Genetic Testing.”

National Institutes of Health: "An Overview of the Human Genome Project."

Clinical Cancer Research: “Detection of Tumor PIK3CA Status in Metastatic Breast Cancer Using Peripheral Blood.”

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