BREAST CAncer (BRCA)
BRCA is the 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.
All individuals have the BRCA1 and BRCA2 genes. 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. In some individuals, 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 as well, they can be found below). ***
Research has shown BRCA1 and BRCA2 put carriers at a higher risk of breast cancer. Women who inherit the BRCA1 or BRCA2 gene have a 56 to 87 percent risk of developing breast cancer by the age of 70.
It’s important to note that many women who have a gene mutation never get cancer of any type,
and these genes cause only about seven to 10 percent of breast cancers.
Consider talking to a genetic counselor and/or having genetic testing if you:
Have breast or ovarian cancer and two or more first-degree relatives (parent, sibling or child) or second-degree relatives (grandparent, grandchild, niece, nephew or half-sibling) with either breast or ovarian cancer*
Have breast and/or ovarian cancer and one first- or second-degree blood relative younger than 45 (or pre-menopausal) with breast cancer and/or ovarian cancer at any age*
Have breast and/or ovarian cancer develop before age 45 (or pre-menopausal)*
Have a personal history of triple negative breast cancer diagnosed at age 60 or younger**
Have a personal history of two or more types of cancer*
Have breast and/or ovarian cancer that is bilateral (both sides) or have multiple primary sites of cancer*
Are a man with breast cancer*
Have a first- or second-degree blood relative who is documented as being a BRCA1 or BRCA2 gene carrier*
Have Von Hippel-Lindau disease, or have a family member with Von Hippel-Lindau disease. *
Have a personal history of breast cancer and Ashkenazi (Eastern European) Jewish ancestry**
Have a personal history of prostate cancer or pancreatic cancer with two or more relatives with BRCA-associated cancers**
Have a history of breast cancer at a young age in two or more blood relatives, such as your parents, siblings or children**
GENETIC TESTING
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. Talk to your doctor about next steps for this.
OTHER GENES
Here is a list of other genes besides BRCA1 and BRCA2 that sometimes have abnormal changes that run in families with a strong history of breast cancer and other cancers. Most have been linked to some increase in breast cancer risk; others haven’t yet, but that may change over time.
High risk gene mutations
PALB2: The PALB2 (partner and localizer of BRCA2) gene provides instructions to make a protein that works with the BRCA2 protein to repair damaged DNA and stop tumor growth. Research suggests that women with a PALB2 mutation have a 14% risk of developing breast cancer by age 50, but that risk jumps to 35% by age 70. And for those with a family history, the risk of breast cancer by age 70 is 58%.
(In comparison, women with an abnormal BRCA1 gene have a 50% to 70% risk of developing breast cancer by age 70. Women with an abnormal BRCA2 gene have a 40% to 60% risk of developing breast cancer by age 70.)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. The lifetime breast cancer risk for women with a PTEN mutation is estimated at 25% to 50%, although some studies have reported a higher risk, at 77% to 85%. The average age at diagnosis is 38 to 50 years.
TP53: The TP53 gene provides instructions to the body for making a protein that stops tumor growth. Inheriting an abnormal TP53 gene causes Li-Fraumeni syndrome, a disorder in which people 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).
Moderate to high risk gene mutations
ATM: The ATM gene helps repair damaged DNA. DNA carries genetic information in cells. Inheriting two abnormal copies of this gene causes ataxia-telangiectasia, a rare disease that affects brain development. Inheriting one abnormal ATM gene has been linked to an increased rate of breast cancer and pancreatic cancer in some families. That’s because the abnormal gene stops the cells from repairing damaged DNA.
CDH1: The CDH1 gene makes a protein that helps cells bind together to form tissue. An abnormal CDH1 gene increases the risk of a rare type of stomach cancer at an early age. The lifetime risk for this stomach cancer is up to 83%. Women with an abnormal CDH1 gene also have a 39% to 52% lifetime risk of invasive lobular breast cancer.
Moderate risk gene mutations
CHEK2: The CHEK2 gene provides instructions for making a protein that stops tumor growth. An abnormal CHEK2 gene can at least double the lifetime risk of breast cancer. It can also increase colorectal and prostate cancer risk.
NBN: The NBN gene controls production of a protein called nibrin, which helps repair DNA damage in cells. An abnormal NBN gene causes Nijmegen breakage syndrome, a condition that results in slow growth in infancy and early childhood.
NF1: An NF1 mutation causes a condition called neurofibromatosis type 1, which increases the risk of central nervous system cancers and a specific type of cancer that grows in the wall of the stomach or intestines, called gastrointestinal stromal tumors. The lifetime risk of cancer overall is nearly 60%. Some studies have suggested that women with an NF1 mutation are at higher risk of developing breast cancer, especially before age 50.
STK11: The STK11 gene helps regulate cell growth. An abnormal STK11 gene causes Peutz-Jeghers 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. In addition to gastrointestinal cancers, people with Peutz-Jeghers syndrome are also at higher risk of breast cancer, lung cancer, and ovarian tumors. People with Peutz-Jeghers syndrome may also develop freckling around the eyes, nose, and mouth, as well as inside the mouth.
Genetic mutations with uncertain breast cancer risk
Other gene mutations are sometimes found in families with a strong history of cancer. Mutations in the genes listed below may or may not cause an increased risk of breast cancer. Further research is needed to tell what the increased breast cancer risk is, if any.
BARD1: BARD1 (BRCA1 Associated Ring Domain 1) is a gene that works with BRCA1 to repair damaged DNA. Some studies have suggested that BARD1 mutations can increase breast cancer risk.
BRIP1: The BRIP1 gene also works to repair DNA. Right now, a BRIP1 mutation is associated with a higher lifetime risk of ovarian cancer. There is not enough evidence to link it with increased breast cancer risk.
MLH1, MSH2, MSH6, PMS2, EPCAM: All of these are called mismatch repair genes, and they work to repair any mistakes that occur when DNA copies itself. Inherited mutations in these genes lead to a condition known as Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC). People with Lynch syndrome are at higher risk of colorectal cancer and other cancers, including endometrial and ovarian cancer.
RAD51C and RAD51D: These genes are involved in repairing DNA damage. Both have been linked to a small increase in the lifetime risk of ovarian cancer. They have not been linked to elevated breast cancer risk.