BRCA: BReast CAncer gene

BRCA” is an abbreviation for “BReast CAncer gene.” BRCA1 and BRCA2 are the two most common genes that have been found to impact a person’s chances of developing breast cancer.

Every individuals has both the BRCA1 and BRCA2 genes. Despite what their names might suggest, BRCA genes do not cause breast cancer. In fact, these genes normally play a large role in preventing breast cancer. They help repair DNA breaks that can lead to cancer and the uncontrolled growth of tumors. Because of this, the BRCA genes are known as tumor suppressor genes.

However, in some these tumor suppression genes do not work properly. When a gene becomes altered or broken, it doesn’t function correctly. This is called a gene mutation. There are various other genes which cause a predisposition to breast cancer, you can find them listed in a tab below. 

A small percentage of people (about one in 400, or 0.25% of the population) carry mutated BRCA1 or BRCA2 genes. A BRCA mutation occurs when the DNA that makes up the gene becomes damaged in some way.

When a BRCA gene is mutated, it may no longer be effective at repairing broken DNA and helping to prevent breast cancer. Because of this, people with a BRCA gene mutation are more likely to develop breast cancer, and more likely to develop cancer at a younger age. The carrier of the mutated gene can also pass a gene mutation down to his or her offspring.

It’s estimated that 55 – 65% of women with the BRCA1 mutation will develop breast cancer before age 70.

Approximately 45% of women with a BRCA2 mutation will develop breast cancer by age 70.

Women with a BRCA1 or BRCA2 mutation also have a higher-than-average chance of experiencing breast cancer reoccurrence. Cancers related to a BRCA1 mutation are also more likely to be triple negative breast cancer, which can be more aggressive and difficult to treat.

It’s important to note, however, that less than 10% of women diagnosed with breast cancer have a BRCA mutation. Also, with early detection, the vast majority of breast cancer cases can be successfully treated—and that’s true even for people who have a BRCA1 or BRCA2 mutation. Many women with a BRCA mutation choose to undergo a preventative mastectomy to reduce their risk of developing breast cancer. You can learn more about your options here.

Genetic tests are available to detect BRCA1 and BRCA2 mutations. DNA (usually from a blood or saliva sample) is needed for these tests. The sample is sent to a laboratory for analysis. It usually takes about a month to get the test results.

Some tests look for a specific harmful BRCA1 or BRCA2 gene mutation that has already been identified in another family member. Other tests check for all of the known harmful mutations in both genes. Multigene (panel) testing uses next-generation sequencing to look for harmful mutations in many genes that are associated with an increased risk of breast and ovarian cancer, including BRCA1 and BRCA2, at the same time.

Mutations in other genes are also associated with breast cancer. These genetic mutations are less common and do not seem to increase risk as much as BRCA1 and BRCA2 mutations (which are also considered rare). Genetic tests are available to detect these mutations (generally via a blood or saliva sample).

  • ATM: The ATM gene helps repair damaged DNA. DNA carries genetic information in cells. Inheriting two mutated copies of this gene causes the disease ataxia-telangiectasia, a rare disease that affects brain development. Inheriting one mutated ATM gene has been linked to an increased rate of breast cancer and pancreatic cancer in some families because the mutation stops the cells from repairing damaged DNA.
  • BARD1: The BARD1 gene works with the BRCA1 gene to repair DNA damage. A mutation in the BARD1 gene increases a woman’s risk of breast cancer. Researchers are studying whether a BARD1 mutation also increases the risk of ovarian cancer.
  • BRIP1: The BRIP1 gene also works to repair DNA. Inheriting one mutated BRIP1 gene is associated with higher risk of both breast and ovarian cancer.
  • CDH1: The CDH1 gene makes a protein that helps cells bind together to form tissue. A mutated CDH1 gene increases the risk of a rare type of stomach cancer at an early age. The lifetime risk is up to 83%. Women with a CDH1 mutation also have a 39% to 52% lifetime risk of invasive lobular breast cancer.
  • CHEK2: The CHEK2 gene provides instructions for making a protein that stops tumor growth. A CHEK2 mutation can at least double breast cancer risk, double colon cancer risk, and increase prostate cancer risk.
  • MRE11A: Along with the RAD50 and NBN genes, the MRE11A gene forms the MRN complex, which helps repair DNA damage in cells. An MRE11A mutation 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.
  • MSH6: The MSH6 gene provides instructions for making a protein that helps repair DNA damage. Studies have found that mutations in the MSH6 gene are linked to Lynch syndrome and a higher risk of ovarian cancer. Having Lynch syndrome increases the risk of many types of cancer, particularly colorectal, endometrial, ovarian, stomach, small intestine, liver, gallbladder, upper urinary tract, and brain. In 2018, research found that women with a MSH6 mutation had double the breast cancer risk of the average woman.
  • NBN: Along with the MRE11A and RAD50 genes, the NBN gene forms the MRN complex, which helps repair DNA damage in cells. An NBN mutation 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 NBN mutation has the strongest link to 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 a PALB2 mutation increases breast cancer risk 5 to 9 times higher than average, almost as high as a BRCA1 or BRCA2 mutation. Women with a PALB2 mutation have a 33% to 58% lifetime risk of developing breast cancer. In comparison, women with a BRCA1 mutation have a 50% to 70% risk of developing breast cancer by age 70. Women with a BRCA2 mutation have a 40% to 60% risk of developing breast cancer by age 70.
  • PMS2: The PMS2 gene provides instructions for making a protein that helps repair DNA damage. Studies have found that mutations in the PMS2 gene are linked to Lynch syndrome and a higher risk of ovarian cancer. Having Lynch syndrome increases the risk of many types of cancer, particularly colorectal, endometrial, ovarian, stomach, small intestine, liver, gallbladder, upper urinary tract, and brain. In 2018, research found that women with a PMS2 mutation had double the breast cancer risk of the average woman.
  • PTEN: The PTEN gene helps regulate cell growth. A PTEN mutation 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. The lifetime breast cancer risk for women with a PTEN mutation is up to 85%.In 2015, a SEC23B mutation also was linked to Cowden syndrome. The SEC23B gene also helps regulate cell growth.
  • RAD50: Along with the MRE11A and NBN genes, the RAD50 gene forms the MRN complex, which helps repair DNA damage in cells. An RAD50 mutation has been linked to a higher risk of breast cancer in some families because the abnormal gene stops the cells from repairing damaged DNA.
  • RAD51C: The RAD51C gene repairs DNA damage. People who have inherited one mutated copy have higher risk of breast and ovarian cancer.
  • STK11: The STK11 gene helps regulate cell growth. An STK11 mutation causes Peutz Jegher syndrome, a rare disorder in which people tend to develop a type of polyp, called a hamartomatous polyp, mostly in the small intestine but also in the stomach and colon. People with Peutz Jegher syndrome are at higher risk not only of gastrointestinal cancers, but also breast and lung cancer and ovarian tumors. People may also develop freckling around the eyes, nose, and mouth, as well as inside the mouth.
  • TP53: The TP53 gene provides instructions to the body for making a protein that stops tumor growth. Inheriting a TP53 mutation 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). The cancer risk in women with a TP53 mutation is up to nearly 100%. In men, it is up to 73%. This gender difference is mostly due to the high breast cancer risk in women.

Inheriting two abnormal copies of the BRCA2, BRIP1, MRE11A, NBN, PALB2, RAD50, or RAD51C genes causes the disease Fanconi anema, 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.

Information provided by: www.BreastCancer.org

Want to learn more about your options for preventive mastectomy and reconstruction? Check out our Mastectomy and Reconstruction pages.

Because harmful BRCA1, BRCA2 and other gene mutations are relatively rare in the general population, most experts agree that mutation testing of individuals who do not have cancer should be performed only when the person’s individual or family history suggests the possible presence of a harmful mutation.

The United States Preventive Services Task Force recommends that women who have family members with breast, ovarian, fallopian tube, or peritoneal cancer be evaluated to see if they have a family history that is associated with an increased risk of a harmful mutation in one of these genes.

Several screening tools are available to help health care providers with this evaluation. These tools assess personal or family history factors that are associated with an increased likelihood of having a harmful mutation in BRCA1 or BRCA2, such as:

  • Breast cancer diagnosed before age 50 years
  • Cancer in both breasts in the same woman
  • Both breast and ovarian cancers in either the same woman or the same family
  • Multiple breast cancers in the family
  • Two or more primary types of BRCA1 or BRCA2 related cancers in a single family member
  • Cases of male breast cancer
  • Ashkenazi Jewish ethnicity

When an individual has a family history that is suggestive of the presence of a BRCA1 or BRCA2 mutation, it may be most informative to first test a family member who has cancer, if that person is still alive and willing to be tested. If that person has a harmful BRCA1 or BRCA2 mutation, then other family members may want to consider genetic counseling to learn more about their potential risks and whether genetic testing for mutations in BRCA1 and BRCA2 might be appropriate for them.

If it can’t be determined whether the family member with cancer has a harmful BRCA1 or BRCA2 mutation, members of a family whose history is suggestive of the presence of a BRCA1 or BRCA2 gene mutation may still want to consider genetic counseling for possible testing.

Once you’ve decided to get BRCA tested, you’ll first want to talk to your doctor (for example: your OBGYN), who will help decide if you fit the criteria to receive testing. From there, your doctor can help guide you through the process and even refer you to a genetic counselor. If your doctor isn’t familiar with genetic counseling, there are services that can help find the right counselor for you.

To test for a hereditary BRCA mutation, your doctor or genetic counselor will collect a blood or saliva sample to test your DNA (or through an at home test kit). This sample will be sent to a lab where a technician will look for mutations in your DNA. The lab will then report the results to your doctor or genetic counselor. This process can take a few weeks.

Once your doctor or genetic counselor receives the results, he or she will inform you of your BRCA status. At this point, your doctor may suggest next steps, depending on your status.

Companies that provide at home genetic testing kits:

Color
23andme

If you’ve tested positive for a mutation in the BRCA1 or BRCA2 gene — or some other inherited gene mutation associated with increased risk of breast cancer and possibly other cancers — it’s natural to be concerned about passing the mutation along to your biological children. There’s a 50% chance that any child you have will inherit the mutation. The same holds true if you are not a mutation carrier but your partner is.

Some women of childbearing age are now choosing to use preimplantation genetic testing, or PGT, to ensure they won’t pass a BRCA1 or BRCA2 mutation on to their children. PGT also can be used in cases of other cancer-related mutations. For several years, couples have used preimplantation genetic diagnosis to avoid passing along hereditary diseases such as cystic fibrosis, muscular dystrophy, and Huntington’s disease. But now, some parents are using it to avoid passing along the BRCA1, BRCA2 and other mutations.

PGT can offer parents (and their future children) peace of mind. The first step is going through the process called in-vitro fertilization, or IVF. With IVF, a woman takes medications to stimulate her ovaries to produce multiple eggs. The eggs are removed and fertilized outside the body in a test tube. Successfully fertilized eggs then become embryos.

After a few days, PGT can be performed: One or two cells can be removed from each embryo and tested for the particular BRCA1 or BRCA2 mutation carried by the parent. The couple or mother can then choose only healthy, BRCA-mutation-free embryos to be implanted in the uterus and/or stored for future use.

Shady Grove Fertility on Genetic Diagnosis