← Breastcancer.org

Genetics


About 5% to 10% of breast cancers are thought to be hereditary, caused by abnormal genes passed from parent to child.

Genes are particles in cells, contained in chromosomes, and made of DNA (deoxyribonucleic acid). DNA contains the instructions for building proteins. And proteins control the structure and function of all the cells that make up your body.

Think of your genes as an instruction manual for cell growth and function. Abnormalities in the DNA are like typographical errors. They may provide the wrong set of instructions, leading to faulty cell growth or function. In any one person, if there is an error in a gene, that same mistake will appear in all the cells that contain the same gene. This is like having an instruction manual in which all the copies have the same typographical error.

BRCA1 and BRCA2 genes

Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two).

Everyone has BRCA1 and BRCA2 genes. The function of the BRCA genes is to repair cell damage and keep breast cells growing normally. But when these genes contain abnormalities or mutations that are passed from generation to generation, the genes don't function normally and breast cancer risk increases. Abnormal BRCA1 and BRCA2 genes may account for up to 10% of all breast cancers, or 1 out of every 10 cases.

Having an abnormal BRCA1 or BRCA2 gene doesn't mean you will be diagnosed with breast cancer. Researchers are learning that other mutations in pieces of chromosomes -- called SNPs (single nucleotide polymorphisms) -- may be linked to higher breast cancer risk in women with an abnormal BRCA1 gene as well as women who didn't inherit an abnormal breast cancer gene.

Women who are diagnosed with breast cancer and have an abnormal BRCA1 or BRCA2 gene often have a family history of breast cancer, ovarian cancer, and other cancers. Still, most people who develop breast cancer did not inherit an abnormal breast cancer gene and have no family history of the disease.

You are substantially more likely to have an abnormal breast cancer gene if:

  • You have blood relatives (grandmothers, mother, sisters, aunts) on either your mother's or father's side of the family who had breast cancer diagnosed before age 50.
  • There is both breast and ovarian cancer in your family, particularly in a single individual.
  • There are other gland-related cancers in your family such as pancreatic, colon, and thyroid cancers.
  • Women in your family have had cancer in both breasts.
  • You are of Ashkenazi Jewish (Eastern European) heritage.
  • You are African American and have been diagnosed with breast cancer at age 35 or younger.
  • A man in your family has had breast cancer.

If one family member has an abnormal breast cancer gene, it does not mean that all family members will have it.

The average woman in the United States has about a 1 in 8, or a 12-13%, risk of developing breast cancer in her lifetime. Women who have an abnormal BRCA1 or BRCA2 gene (or both) can have up to an 80% risk of being diagnosed with breast cancer during their lifetimes. Breast cancers associated with an abnormal BRCA1 or BRCA2 gene tend to develop in younger women and occur more often in both breasts than cancers in women without these abnormal genes.

Women with an abnormal BRCA1 or BRCA2 gene also have an increased risk of developing ovarian, colon, pancreatic, and thyroid cancers, as well as melanoma.

Men who have an abnormal BRCA2 gene have a higher risk for breast cancer than men who don't -- about 8% by the time they're 80 years old. This is about 80 times greater than average.

Men with an abnormal BRCA1 gene have a slightly higher risk of prostate cancer. Men with an abnormal BRCA2 gene are 7 times more likely than men without the abnormal gene to develop prostate cancer. Other cancer risks, such as cancer of the skin or digestive tract, also may be slightly higher in men with abnormal BRCA1 or BRCA2 genes.

Other genes

Changes in other genes are also associated with breast cancer. These abnormal genes are much less common and don't seem to increase risk as much as abnormal BRCA1 and BRCA2 genes, which are considered rare. Still, because these genetic mutations are rarer, they haven't been studied as much as the BRCA genes.

  • ATM: The ATM gene helps repair damaged DNA. DNA carries genetic information in cells. Inheriting two abnormal copies of this gene causes the disease ataxia-telangiectasia, a rare disease that affects brain development. Inheriting one abnormal ATM gene has been linked to an increased rate of breast cancer in some families because the abnormal gene stops the cells from repairing damaged DNA.
  • p53 (also called the TP53 gene): The p53 gene provides instructions to the body for making a protein that stops tumor growth. Inheriting an abnormal p53 gene causes Li-Fraumeni syndrome, a disorder that causes people to develop soft tissue cancers at a young age. People with this rare syndrome have a higher-than-average-risk of breast cancer and several other cancers, including leukemia, brain tumors, and sarcomas (cancer of the bones or connective tissue).
  • CHEK2: The CHEK2 gene also provides instructions for making a protein that stops tumor growth. Li-Fraumeni syndrome also can be caused by an inherited abnormal CHEK2 gene. Even when an abnormal CHEK2 gene doesn't cause Li-Fraumeni syndrome, it can double breast cancer risk.
  • PTEN: The PTEN gene helps regulate cell growth. An abnormal PTEN gene causes Cowden syndrome, a rare disorder in which people have a higher risk of both benign (not cancer) and cancerous breast tumors, as well as growths in the digestive tract, thyroid, uterus, and ovaries.
  • CDH1: The CDH1 gene makes a protein that helps cells bind together to form tissue. An abnormal CDH1 gene causes a rare type of stomach cancer at an early age. Women with an abnormal CDH1 gene also have an increased risk of invasive lobular breast cancer.
  • PALB2: The PALB2 gene is called the partner and localizer of BRCA2. It provides instructions to make a protein that works with the BRCA2 protein to repair damaged DNA and stop tumor growth. Research published in 2014 found that an abnormal PALB2 gene increases breast cancer 5 to 9 times higher than average, almost as high as an abnormal BRCA1 or BRCA2 gene. Women with an abnormal PALB2 gene have a 14% risk of developing breast cancer by age 50 and a 35% risk of developing breast cancer by age 70. In comparison, women with an abnormal BRCA1 gene have a 50%-70% risk of developing breast cancer by age 70. Women with an abnormal BRCA2 gene have a 40%-60% risk of developing breast cancer by age 70.

    Inheriting two abnormal PALB2 genes causes Fanconi anemia type N, which suppresses bone marrow function and leads to extremely low levels of red blood cells, white blood cells, and platelets. People with Fanconi anemia also have a higher risk of several other types of cancer, including kidney cancer and brain cancer.
  • RINT1: The RINT1 gene, also called RAD50 interactor 1, helps regulate cell division. Besides breast cancer, an abnormal RINT1 gene is linked to Lynch-syndrome cancers: cancer of the colon, rectum, stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, ovaries, lining of the uterus, and skin.
  • MRE11A: Along with the RAD50 and NBN genes, the MRE11A gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal MRE11A gene is linked to ataxia-telangiectasia-like disorder, a rare disease that affects brain development. The disease also weakens the immune system and increases cancer risk.
  • RAD50: Along with the MRE11A and NBN genes, the RAD50 gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal RAD50 gene has been linked to a higher risk of breast cancer in some families because the abnormal gene stops the cells from repairing damaged DNA.
  • NBN: Along with the MRE11A and RAD50 genes, the NBN gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal NBN gene causes Nijmegen breakage syndrome, a condition that causes slow growth in infancy and early childhood. People with Nijmegen breakage syndrome are shorter than average, have a higher risk of several types of cancer, including breast cancer, and many other health problems. Of the three genes in the MRN complex, researchers think that an abnormal NBN has the strongest link to breast cancer.

Genetic testing

There are genetic tests available to determine if someone has an abnormal BRCA1 or BRCA2 gene. A genetic counselor also may order testing for an abnormal ATM, p53, CHEK2, PTEN, CDH1, PALB2, RINT1, MRE11A, RAD50, or NBN gene if it's determined from your personal or family history that these tests are needed.

For more information, visit the Breastcancer.org Genetic Testing pages.

Steps you can take

If you know you have an abnormal gene linked to breast cancer, there are lifestyle choices you can make to keep your risk as low it can be:

These are just a few steps you can take. Review the links on the left side of this page for more options.

Along with these lifestyle choices, there other risk-reduction options for women at high risk because of abnormal genetics.

Hormonal therapy medicines: Two SERMs (selective estrogen receptor modulators) and two aromatase inhibitors have been shown to reduce the risk of developing hormone-receptor-positive breast cancer in women at high risk.

  • Tamoxifen has been shown to reduce the risk of first-time hormone-receptor-positive breast cancer in both postmenopausal and premenopausal women at high risk. Certain medicines may interfere with tamoxifen's protective effects. Visit the Tamoxifen page to learn more.
  • Evista (chemical name: raloxifene) has been shown to reduce the risk of first-time hormone-receptor-positive breast cancer in postmenopausal women. Visit the Evista page to learn more.
  • Aromasin (chemical name: exemestane), an aromatase inhibitor, has been shown to reduce the risk of first-time hormone-receptor-positive breast cancer in postmenopausal women at high risk. Aromasin isn’t approved by the FDA for this use, but doctors may consider it a good alternative to tamoxifen or Evista. In 2013, the American Society of Clinical Oncology (ASCO) released new guidelines on using hormonal therapy medicines to reduce breast cancer risk in high-risk women. These guidelines recommend that doctors talk to high-risk postmenopausal women about using Aromasin to reduce risk. ASCO is a national organization of oncologists and other cancer care providers. ASCO guidelines give doctors recommendations for treatments that are supported by much credible research and experience. Visit the Aromasin page for more information.
  • Arimidex (chemical name: anastrozole), also an aromatase inhibitor, has been shown to reduce the risk of first-time, hormone-receptor-positive breast cancer in postmenopausal women at high risk. Like Aromasin, Arimidex isn’t approved by the FDA for this use, but doctors may consider it a good alternative to tamoxifen, Evista, or Aromasin. Visit the Arimidex page for more information.

Hormonal therapy medicines do not reduce the risk of hormone-receptor-negative breast cancer.

More frequent screening: If you're at high risk because of an abnormal breast cancer gene, you and your doctor will develop a screening plan tailored to your unique situation. You may start being screened when you're younger than 40. In addition to the recommended screening guidelines for women at average risk, a screening plan for a woman at high risk may include:

Women with an abnormal breast cancer gene need to be screened twice a year because they have a much higher risk of cancer developing in the time between yearly screenings. For example, the Memorial Sloan-Kettering Cancer Center in New York, NY recommends that women with an abnormal BRCA1 or BRCA2 gene have both a digital mammogram and an MRI scan each year, about 6 months apart (say a mammogram in January and an MRI in June).

A breast ultrasound is another powerful tool that can help detect breast cancer in women with an abnormal breast cancer gene. This test does not take the place of digital mammography and MRI scanning.

Talk to your doctor, radiologist, and genetic counselor about developing a specialized program for early detection that addresses your breast cancer risk, meets your individual needs, and gives you peace of mind.

Protective surgery: Removing the healthy breasts and ovaries -- called prophylactic surgery ("prophylactic" means "protective") -- are very aggressive, irreversible risk-reduction options that some women with an abnormal BRCA1 or BRCA2 gene choose.

Prophylactic breast surgery may be able to reduce a woman's risk of developing breast cancer by as much as 97%. The surgery removes nearly all of the breast tissue, so there are very few breast cells left behind that could develop into a cancer.

Women with an abnormal BRCA1 or BRCA2 gene may reduce their risk of breast cancer by about 50% by having prophylactic ovary removal (oophorectomy) before menopause. Removing the ovaries lowers the risk of breast cancer because the ovaries are the main source of estrogen in a premenopausal woman’s body. Removing the ovaries doesn’t reduce the risk of breast cancer in postmenopausal women because fat and muscle tissue are the main producers of estrogen in these women. Prophylactic removal of both ovaries and fallopian tubes reduces the risk of ovarian cancer in women at any age, before or after menopause.

Research also has shown that women with an abnormal BRCA1 or BRCA2 gene who have prophylactic ovary removal have better survival if they eventually are diagnosed with breast or ovarian cancer.

The benefit of prophylactic surgeries is usually counted one year at a time. That’s why the younger you are at the time of surgery, the larger the potential benefit and the older you are, the lower the benefit. Also, as you get older you’re more likely to develop other medical conditions that affect how long you live, such as diabetes and heart disease.

Of course, each woman's situation is unique. Talk to your doctor about your personal level of risk and how best to manage it.

It's important to remember that no procedure -- not even removing both healthy breasts and ovaries at a young age -- totally eliminates the risk of cancer. There is still a small risk that cancer can develop in the areas where the breasts used to be. Close follow-up is necessary, even after prophylactic surgery.

Prophylactic surgery decisions require a great deal of thought, patience, and discussion with your doctors, genetic counselor, and family over time -- together with a tremendous amount of courage. Take the time you need to consider these options and make decisions that feel comfortable to you.

For more information visit the Breastcancer.org Prophylactic Mastectomy and Prophylactic Ovary Removal pages.


TPLG Booklet ThumbnailThink Pink, Live Green: A Step-by-Step Guide to Reducing Your Risk of Breast Cancer teaches you the biology of breast development and how modern life affects breast cancer risk. Order a free booklet by mail or download the PDF of the booklet to learn 31 risk-reducing steps you can take today.

Evergreen-donate
Back to Top