What is BRCA1 and BRCA2 Mutations (Breast Cancer Gene Mutations)?
One in every eight women (about 12.5%) in the United States will get breast cancer at some point in their lives. Some people have a higher risk of getting this disease because of their genetic make-up. BRCA1 and BRCA2 are genes that, if they mutate or change, can increase the chance of getting certain types of cancer, particularly breast and ovarian cancer. These genetic changes are responsible for 5% to 10% of all breast cancer cases. If a person inherits the mutated BRCA1 or BRCA2 genes, they have a condition known as Hereditary Breast and Ovarian Cancer syndrome (HBOC). This inherited gene mutation accounts for about half of the cancer cases linked to genetic risk.
In recent years, we have gotten better at recognizing genetic risks for cancer, understanding which patients are at high risk, and giving these patients the right tests. This means we are now much better at identifying which patients are at risk, screening them early, and preventing cancer. If a patient is found to have a mutated BRCA1 or BRCA2 gene, their treatment will be personalized. It may include more regular check-ups, using preventative medicine like tamoxifen, or preventative surgery such as removing both ovaries or both breasts.
The most common cancers linked to mutated BRCA1 and BRCA2 genes are ovarian and breast cancer.
What Causes BRCA1 and BRCA2 Mutations (Breast Cancer Gene Mutations)?
Mutations in the BRCA1 or BRCA2 genes are not very common, occurring in about 1 in every 300 to 800 people. However, some groups have a higher chance of having these genetic changes. These include people of Ashkenazi Jewish descent, men who develop breast cancer, and patients under the age of 30 who develop breast cancer.
There are certain gene mutations that are more frequently passed down in families descendant from the same genetic lineage; these are called founder mutations. Specific types of these mutations are more common in the Ashkenazi Jewish community, including the 185delAG and 5385insC mutations in the BRCA1 gene and 6174delT mutation in the BRCA2 gene.
The BRCA1 and BRCA2 gene mutations significantly increase the risk of developing certain types of cancer. The risk of breast cancer is the highest, affecting 40% to 80% of people with these gene mutations. There is also a higher chance of developing other types of cancer like ovarian, pancreatic, and prostate cancer.
Risk Factors and Frequency for BRCA1 and BRCA2 Mutations (Breast Cancer Gene Mutations)
Everyone has some level of risk of developing cancer. For example, in the general population the risk of developing breast cancer is 12.5% for women and 0.1% for men, and there’s a 1-2% chance of developing ovarian cancer. However, if you have a BRCA1 or BRCA2 mutation, your risk is higher. Here is how these mutations might affect your cancer risk by the time you’re 70:
- BRCA1 Mutation
- Around 35% of inherited breast cancer cases come from this mutation
- The risk of developing breast cancer by age 70 jumps to between 44% and 78%
- The risk of developing ovarian cancer by age 70 climbs to between 18% and 54%
- The risk of a man developing breast cancer by age 70 increases to between 0.22% and 2.8%
- BRCA2 Mutation
- About 25% of inherited breast cancer cases are due to this mutation
- The risk of developing breast cancer by age 70 rises to between 31% and 56%
- The risk of developing ovarian cancer by age 70 increases to between 2.4% and 19%
- The risk of a man developing breast cancer by age 70 goes up to between 3.2% and 12%
Signs and Symptoms of BRCA1 and BRCA2 Mutations (Breast Cancer Gene Mutations)
The United States Preventive Service Task Force advises family doctors to check every year if women are potentially at risk for inherited cancer, based on their family’s history with breast, ovarian and other cancers. If a woman’s family history suggests she may be at risk, she should be referred to a certified genetic counselor. This is considered a Grade B recommendation, meaning it’s highly recommended. Genetic counselors or breast specialists can then help decide if testing for BRCA, a gene associated with breast and ovarian cancer, is needed, or if tests for other genetic mutations linked to different types of inherited cancers are necessary.
About 7% of families with multiple occurrences of breast cancer have the BRCA1 mutation, and around 40% of families with cases of both ovarian and breast cancer carry this mutation. The BRCA2 mutation shows up in about 20% of families at high risk for ovarian and breast cancer. However, less than 3% of women who get breast cancer at an early age have this mutation. The BRCA2 mutation is also associated with other types of cancer, such as:
- Pancreatic cancer
- Prostate cancer
- Stomach cancer
- Bile duct cancer
- Gallbladder cancer
- Melanoma (a potentially deadly type of skin cancer)
Testing for BRCA1 and BRCA2 Mutations (Breast Cancer Gene Mutations)
The American Society of Breast Surgeons and the National Comprehensive Cancer Network (NCCN) have developed guidelines for genetic risk assessment for breast cancer. These guidelines suggest that certain people should undergo genetic testing, either due to their personal or family history.
Those who’ve previously had breast cancer should consider testing if they meet any of the following criteria:
- Diagnosed before age 50
- Had a specific type of breast cancer (called a triple-negative tumor) and were under 60 years old when diagnosed
- Of Ashkenazi Jewish heritage, with breast cancer at any age
- Diagnosed with two or more primary types of breast cancer
- Have a first-degree relative (like a mother or sister) who had breast cancer diagnosed before age 50
- Two or more relatives from the same side of the family with breast or pancreatic cancer
- Family member with a history of ovarian, fallopian, or primary peritoneal cancer
- Male with breast cancer
- Family member known to carry a mutation related to breast cancer
Even those who haven’t had breast cancer might consider testing if they meet the following criteria:
- A close relative had a breast cancer diagnosis before age 45
- Ashkenazi Jewish heritage and family history of breast cancer
- A family member with two or more types of primary breast cancer
- Multiple relatives from the same side of the family with breast or pancreatic cancer
- History of ovarian, fallopian, or peritoneal cancer in the family
- Male family member with breast cancer
- Known mutation carrier in the family
Doctors might also use risk assessment models, such as BRCAPRO, BOADICEA, Penn II, and IBIS, to help determine if a person is at higher risk of carrying gene mutations related to breast cancer. However, these are only predictions. They should not be the only determining factor for deciding if genetic testing is necessary.
Treatment Options for BRCA1 and BRCA2 Mutations (Breast Cancer Gene Mutations)
People with the BRCA1 and BRCA2 mutations need to carefully and regularly monitor their health to catch any signs of cancer early. National Comprehensive Cancer Network (NCCN) guidelines are usually followed when managing these cases. The main aim is to detect cancer and high-risk lesions before they have a chance to harm the patient. Starting at age 18, this involves being aware of any changes in the breast and doing self-exams, followed by yearly or twice-yearly clinical breast exams from age 25. Even though there’s no clear evidence that these practices significantly improve survival rates, they are still advised.
An MRI scan can be a really useful tool in catching any signs of cancer in people who have a family or genetic predisposition. It can spot cancer about 80% of the time, which is much better than the 33% accuracy rate without the scan. According to the NCCN guidelines, those with BRCA mutations should have an MRI scan with contrast yearly from age 25 to 29 if it’s available. If it’s not, a yearly mammogram should be scheduled. Between age 30 to 75, both annual mammogram and MRI scans should be done.
Depending on the individual needs of the patient with the BRCA1 or BRCA2 mutation, their care plan may include keeping a close eye on their health, using preventative medicines like tamoxifen or raloxifene, or even having preventative surgeries like removal of the fallopian tubes, ovaries, or breasts. A preventative mastectomy can reduce the risk of developing breast cancer by 90% to 95%. Anyone considering this form of risk reduction should talk it through with a breast surgeon.
What else can BRCA1 and BRCA2 Mutations (Breast Cancer Gene Mutations) be?
When checking for causes of breast discomfort or anomaly, doctors usually consider a number of conditions such as:
- Abnormal growths or lumps in the breast
- Breast cancer
- Benign breast lumps, medically known as fibroadenomas
- Ductal carcinoma (breast cancer that begins in the milk ducts)
- Duct ectasia, a non-cancerous condition where a breast duct widens and its walls thicken
- Fibrocystic disease, a benign condition causing lumpiness in one or both breasts
- Hyalinized fibroadenoma, a benign breast lump that has been present for a long period
- Inflammatory breast cancer, a rare form of breast cancer causing redness and swelling
- Mastitis, an infection in the tissue of the breast causing pain, swelling, and redness
- Papilloma, a usually benign, tiny growth in the breast
A proper diagnosis from a doctor helps ensure the best treatment options are considered.
What to expect with BRCA1 and BRCA2 Mutations (Breast Cancer Gene Mutations)
Patients carrying BRCA1 and BRCA2 mutations tend to have a lower survival rate specifically relating to breast cancer, compared to patients who don’t have these mutations. Among mutation carriers, those with BRCA1 have a lower survival rate than those with BRCA2.
Research has shown that women with BRCA mutations are at a higher risk of developing secondary cancer – this could be in the same breast or the other one. It is for this reason that these women are usually advised to undergo a preventive double mastectomy. Interestingly, it’s been found that women who do have this procedure are less likely to die from breast cancer than those who only have a single-breast mastectomy.
