Test Results for BRCA1, BRCA2, and Other Gene Mutations
You’ve probably heard of the genes BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2). Despite their names, these genes actually help stop cells from growing and dividing too fast or in an uncontrolled way.
Everyone has two copies of these genes — one copy inherited from each parent. If one of your parents has a BRCA gene mutation, you have a 50% chance of inheriting a copy of the mutated gene.
If BRCA1, BRCA2, or both genes have a mutation, the genes have a harder time stopping out of control cell growth. This can lead to cancer.
Studies have found more than 3,700 mutations linked to disease in the BRCA genes, especially breast and ovarian cancer. People with a BRCA mutation also tend to develop cancer at a younger age than people without a mutation.
If you test positive for a BRCA mutation or other mutation linked to breast cancer, you can pass that mutation to any children you might have. Each child has a 50% risk of inheriting the cancer-related mutation. All your blood relatives also have an increased risk of having the same gene mutation. For example, if you test positive for a BRCA1 or BRCA2 mutation, your full siblings have a 50% risk of also having the same BRCA mutation.
Some doctors use the term “hereditary breast and ovarian cancer syndrome,” or HBOC, when people inherit a BRCA mutation.
Still, not everyone with a BRCA mutation develops cancer.
BRCA mutations in certain racial and ethnic groups
Certain BRCA mutations are more common in people of certain racial or ethnic backgrounds. For example, about 2% of people of Ashkenazi Jewish descent inherit specific types of BRCA mutations. Black people in the United States tend to have BRCA mutations that aren’t common in other racial or ethnic groups.
BRCA mutations and breast cancer risk
According to the U.S. National Cancer Institute and the National Comprehensive Cancer Network, 60%–72% of women with a BRCA1 mutation and 55%–69% with a BRCA2 mutation will develop breast cancer during their lifetimes. In comparison, about 13% of women in the general population will develop breast cancer during their lifetimes. People with a BRCA1 mutation are more likely to develop triple-negative breast cancer.
If a woman with a BRCA mutation is diagnosed with breast cancer, she has a higher risk of developing breast cancer in the opposite breast, called contralateral breast cancer by doctors. In the 20 years after their first diagnosis, about 30%-40% of women with a BRCA1 mutation and about 25% of women with a BRCA2 mutation will develop cancer in the opposite breast. Up to 10% of women without a BRCA mutation will develop contralateral breast cancer.
Up to 1.2% of men with a BRCA1 mutation and between 1.8% and 7.1% with a BRCA2 mutation will develop breast cancer by age 70. Only about 0.1% of men in the general population develop breast cancer by age 70.
Research also shows that people with a BRCA1 or BRCA2 mutation with a history of breast cancer have a higher risk of developing a second primary cancer than people without the mutation.
BRCA mutations and other cancers
BRCA mutations and ovarian cancer risk
Between 39% and 58% of women with a BRCA1 mutation and 13% to 29% of women with a BRCA2 mutation will develop ovarian cancer during their lifetimes. This includes fallopian tube cancer and primary peritoneal cancer (abdominal lining) cancer. About 1.1% of women in the general population will develop ovarian cancer during their lifetimes.
BRCA mutations and prostate cancer risk
Between 7% and 26% of men with a BRCA1 mutation and 19%-61% with a BRCA2 mutation will develop prostate cancer by age 80, compared to about 10.6% of men in the general population.
BRCA mutations and pancreatic cancer risk
Up to 5% of people with a BRCA1 mutation and between 5% and 10% of people with a BRCA2 mutation will develop pancreatic cancer during their lifetimes, compared to about 1.7% of people in the general population.
BRCA mutations and Franconi anemia risk
People who inherit mutations in both copies of their BRCA1 or BRCA2 genes may develop types of Franconi anemia, a rare syndrome linked to developing solid tumors and acute myeloid leukemia, a type of blood cancer, often in childhood.
Testing positive for other gene mutations linked to breast cancer
CDH1 mutations
Women with a CDH1 mutation can have up to a 55% lifetime risk of invasive lobular breast cancer. People with CDH1 mutations also have a higher risk of developing diffuse gastric cancer, a rare type of stomach cancer.
CHEK2 mutations
Women with a CHEK2 mutation have about double the average risk of developing breast cancer. Research suggests that this mutation also raises the risk of male breast cancer and prostate cancer.
PALB2 mutations
Women with a PALB2 mutation and a family history of breast cancer have up to a 60% risk of developing breast cancer over their lifetimes. Women without family history have a 30-40% lifetime risk of breast cancer.
A PALB2 mutation is also associated with a higher risk of ovarian and pancreatic cancers, as well as breast cancer in men.
STK11 mutations
An STK11 mutation causes Peutz-Jeghers syndrome — a rare disorder in which people tend to develop a type of polyp in the small intestine, stomach, and colon. In addition to being at high risk gastrointestinal cancers, people with Peutz-Jeghers syndrome are also at higher risk of breast, lung, and ovarian cancers.
TP53 mutations
Inheriting a TP53 mutation is linked to Li-Fraumeni syndrome— a rare disorder in which people may develop soft tissue, adrenal, and brain cancers, as well as leukemia at a young age. The risk for some of these cancers last into adulthood. People with Li-Fraumeni syndrome may develop common cancers, such as breast, prostate, and colon, at much earlier-than-average ages.
Steps you can take if your results are positive
If you test positive for a mutation linked to breast cancer, you may be able to:
have more frequent cancer screenings that start at a younger age
have surgery to reduce your risk of breast cancer or ovarian cancer
take medicines to reduce your risk
use this information to help make treatment decisions if you’re ever diagnosed with breast cancer
Screening and testing for early detection
If you test positive for a mutation that increases your risk, you can ask your doctor whether it makes sense to:
start breast cancer screening at a younger age (as young as 25)
have a clinical breast exam every six months in addition to monthly breast self-exams
have screening with MRI in addition to mammography
have screening more often than is recommended for people with an average risk of breast cancer, say alternating between a mammogram and a breast MRI every six months
According to the Basser Center at Penn Medicine, people assigned male at birth who test positive for a BRCA mutation should receive yearly clinical breast exams and start doing breast self-exams at age 35.
If you have ovaries and a BRCA mutation, the American College of Obstetricians and Gynecologists recommends you begin annual pelvic exams at age 25. Some doctors also recommend that between the ages of 30 and 35, you consider annual ovarian cancer screening that includes pelvic ultrasound with an intravaginal probe and blood tests for a special protein called CA-125. The CA-125 protein can be higher than normal in people diagnosed with ovarian cancer. Still, CA-125 can be high in people without cancer, so a CA-125 test alone isn’t definitive.
Overall, it’s important to review the risks, benefits, limitations of ovarian cancer testing with your doctor, or, preferably, a gynecologic oncologist, or gynecologist with expertise in inherited cancer risk.
Risk-reducing surgery
People who test positive for a mutation linked to breast cancer may choose to have a double mastectomy (called bilateral prophylactic mastectomy by doctors) to remove both breasts before cancer has a chance to develop. This is an extremely personal decision.
If you have a BRCA1 or BRCA2 mutation, the National Comprehensive Cancer Network recommends surgery to remove the healthy ovaries and fallopian tubes (called bilateral prophylactic salpingo-oophorectomy by doctors) between certain ages to reduce ovarian cancer risk (35-40 years for BRCA1 and 40-45 years for BRCA2).
While prophylactic mastectomy is an option, prophylactic salingo-oophorectomy is recommended. This is because ovarian cancer is hard to detect in its early stages. Researchers are working to develop non-surgical ways to reduce risk.
It’s important to have regular follow-up visits and monitoring as recommended by your doctor.
Risk-reducing medicines
Some people who don’t want or can’t have risk-reducing surgery may be able to take medicines to lower their risk of breast cancer. Medicines used to lower breast cancer risk include tamoxifen, Evista (chemical name: raloxifene), Arimidex (chemical name: anastrozole), and Aromasin (chemical name: exemestane).
These medicines aren’t for everyone, as they can cause side effects that can affect your quality of life, including menopausal symptoms such as hot flashes. So it’s important to talk to your doctor about whether these medicines make sense for you.
Some doctors recommend women with a BRCA mutation take birth control pills to reduce ovarian cancer risk. Since birth control pills can increase breast cancer risk, it’s important to ask your doctor about the risks and benefits and if this option is right for you.
Breast cancer treatment decisions
Knowing you have a BRCA mutation result can affect your treatment decisions if you’ve been diagnosed with HER2-negative breast cancer that is stage I through stage IV.
Medicines called PARP inhibitors, including Talzenna (chemical name: talazoparib) and Lynparza (chemical name: olaparib) are used to treat HER2-negative breast cancer that has a BRCA1 or BRCA2 mutation.
Testing negative for a mutation linked to breast cancer
There are two ways to interpret a report that says you are negative for a gene mutation linked to breast cancer:
True negative
A true negative is when you don’t have a gene mutation that another family member does have. For example, if you know that your mother has a BRCA1 mutation and you test negative for a BRCA1 mutation, it’s considered a true negative result.
A true negative result means that you have the same risk of developing breast cancer or ovarian cancer as anyone in the general population.
Uninformative (also called indeterminate)
This happens if you test negative for a mutation that no other blood relatives have been tested or have tested negative as well. For example, if you have a strong family history of breast or ovarian cancer, but all of your family members have tested negative for a cancer-related gene mutation, it’s still possible that:
there’s a mutation in another gene that was not tested
there’s a mutation in a gene that researchers haven’t yet linked to cancer
Steps you can take if your results are negative
If you have a true negative result for a mutation linked to breast cancer then your breast cancer risk is the same as people in the general population and you should follow the screening guidelines recommended for them:
having annual or semiannual clinical breast exams, depending on your doctor’s recommendations
doing regular breast self-exams
having annual mammograms starting at age 40
What does it mean if I have a variant of unknown significance?
Your genetic test results may show that you have a variant of uncertain or unknown significance (VUS). This means that you have a mutation, but researchers aren’t sure if there’s a link to breast or other cancers.
If research later finds the VUS you have is linked to increased cancer risk, the lab that performed your genetic testing usually sends an updated report to your doctor or genetic counselor.
