BRCA1 and BRCA2 (Breast Cancer Gene 1 and 2) are genes that create proteins that aid in the repair of DNA damage. Each of these genes can pass down in two copies, one from each parent. BRCA1 and BRCA2 are tumor suppressor genes because they can cause cancer with damaging (or pathogenic) variants (or mutations).
People who inherit deleterious variations in one of these genes have a higher risk of developing a variety of fatalities, including breast and ovarian cancers, as well as a variety of other cancers. People infected with a harmful BRCA1 or BRCA2 variation are more likely to get cancer at a young age than those who don’t.
A deleterious BRCA1 or BRCA2 mutation can pass down from either parent. Each parent who carries a mutation in one of these genes has a 50% probability of inheriting the mutation (or 1 in 2 chance). Inherited mutations, also known as germline mutations or variations, are present in all cells from birth.
Even if the person has acquired a dangerous variant in BRCA1 or BRCA2 from one parent, they would have inherited a standard copy of that gene from the other parent (since embryos with a deadly variant from each parent cannot grow in most situations). However, during a person’s lifespan, the usual copy might be lost or changed in various cells in the body. A somatic alteration is a term for such a transformation. Without working BRCA1 or BRCA2 proteins, cells can expand out of control and become cancerous.
Who should undergo genetic counseling or testing for BRCA variants?
Anyone concerned about the possibility of having a dangerous variation in the BRCA1 or BRCA2 gene should talk to their specialist or a genetic counselor about their worries.
There are tests to see if someone has inherited a dangerous BRCA1 or BRCA2 mutation. However, we don’t recommend testing for the general public at this time. Instead, professional groups advise focusing testing on those more likely to carry a dangerous BRCA1 or BRCA2 variation, such as those with a family history of specific cancers. Both persons without cancer and those who have been diagnosed with cancer may benefit from testing. If you know you have a mutation in one of these genes, you can make efforts to lower the risk or catch cancer early. If they have cancer, the knowledge about their conversion may be crucial in determining the best treatment option.
A risk assessment, in which a person meets with a genetic counselor or other health care provider to discuss factors such as whether their family had cancer, what tumors they had, and when they get their diagnosis report, is usually done before testing. Suppose this assessment indicates that someone is at a higher risk of carrying a dangerous BRCA1 or BRCA2 gene variation. In that case, their genetic counselor can discuss the benefits and risks of testing with them and, if they choose, arrange the relevant genetic test.
Direct-to-consumer (DTC) genetic testing may be an option for certain people. For those individuals, genetic counseling indicates to assist them in comprehending the test results and ensure that people undergo the most practical test. People should know that DTC testing isn’t always comprehensive, as they don’t check for all of the dangerous mutations in both genomes. So a negative DTC test result doesn’t necessarily mean they don’t have a hazardous BRCA1 or BRCA2 mutation.
The Preventive Services Task Force of the USA Exit Disclaimer advises risk assessment and follow-up genetic counseling for women with a personal or family history of breast, ovarian, fallopian tube, or peritoneal cancer, or whose heritage is linked to have harmful BRCA1 and BRCA2 mutations.
The National Comprehensive Cancer Network (NCCN) has established criteria for genetic testing of BRCA1 and BRCA2 and several additional genes (such as CDH1, PALB2, PTEN, and TP53) linked to an elevated risk of breast and ovarian cancer.
- People have a family history with any blood relative with a known or likely harmful variant in any of these genes.
- Who got a cancer diagnosis at a younger age, people with two or more cancer examinations, or families with multiple instances of cancer
- Or who have certain acquired cancer predisposition disorders should all undergo risk assessment, according to the NCCN?
Regardless of their disease’s clinical aspects or family history, the ASCO (American Society of Clinical Oncology) suggests that all women diagnosed with epithelial ovarian cancer offer genetic testing for hereditary mutations in BRCA1, BRCA2, and ovarian cancer susceptibility genes.
Professional societies advise against genetic testing for BRCA1 and BRCA2 mutations in children under the age of 18. This is because there are no special risk-reduction efforts for children, and children are doubtful to acquire cancer due to an inherited BRCA variation.
The experts can use a blood sample or a saliva sample to test for inherited BRCA1 and BRCA2 mutations. This is the case because blood cells and salivary cells, like every other cell in the body, possess the BRCA1 and BRCA2 genes. When a person’s tumor gets an examination to see if they are a candidate for treatment with specific targeted therapy, they may discover that they have a BRCA1 or BRCA2 mutation. Because damaging BRCA variations in the tumor could be somatic or germline in origin, anyone with such a variant should consider getting a germline genetic (blood) test to see if the variant was inherited.
When a family history shows that someone without cancer may have inherited a dangerous variation in BRCA1 or BRCA2, it’s ideal for testing a family member who has already been diagnosed with cancer if that person is alive and willing. If such testing shows a known dangerous variant, the individual will have to undergo that variant, giving a clear indicator if they also possess it. Suppose all cancer-affected family members have died or are reluctant or unable to receive genetic testing. In that case, family members who have not been diagnosed with cancer may still be helpful and informative.
What do BRCA1 and BRCA2 genetic test results mean?
A positive, negative, or a variation of uncertain significance (VUS) result can all be from BRCA1 and BRCA2 mutation testing.
- A positive result means a person has inherited a known detrimental mutation in BRCA1 or BRCA2 (commonly known as “pathogenic” or “possibly pathogenic” variants on laboratory test reports) and is at a higher risk of getting specific cancers. On the other hand, a positive result cannot predict whether or not the person will get cancer. Some persons with a cancer-causing BRCA1 or BRCA2 mutation never get cancer.
- A negative test result might signify a variety of things depending on the person who underwent a test due to personal and family medical history and whether or not a detrimental mutation has already been detected in the family. A negative test result suggests the tested person did not inherit the damaging variant in the family and cannot pass it on to their children if the tested person’s close/ blood relative is known to carry a hazardous BRCA1 or BRCA2 variant.
How can someone who inherited a harmful BRCA1 or BRCA2 gene variant reduce their cancer risk?
There are several strategies for lowering cancer risk in those who have inherited a harmful BRCA1 or BRCA2 variation. Some of these options are enhanced screening, risk-reducing surgery (often known as preventive surgery), and chemoprevention.
Screening is improvable. Some women who test positive for deleterious BRCA1 and BRCA2 mutations may opt to begin breast cancer screening at a younger age, have more frequent screening than is suggested for women with an average risk of breast cancer, or undergo MRI screening in addition to mammography.
There are currently no effective ovarian cancer screening technologies available. Doctors often recommend a transvaginal ultrasound, blood testing for the CA-125 antigen, and clinical examinations for ovarian cancer screening in ladies with harmful BRCA1 BRCA2 mutations by some organizations. None of these approaches, however, appear to detect ovarian cancers early enough to increase long-term survival.
The benefits of screening males for breast and other cancers if they have dangerous mutations in BRCA1 or BRCA2 remain unknown. Starting at 35, specific professional groups recommend that such men have annual clinical breast exams. According to the NCCN or National Comprehensive Cancer Network, men with deleterious germline mutations in BRCA1 or BRCA2 should talk to their oncologist’s doctor about PSA or prostate-specific antigen testing for prostate cancer screening starting at age 40. National Comprehensive Cancer Network (NCCN) guidelines.
In persons who are known to carry a harmful BRCA1/ BRCA2 variation and have a close blood family with pancreatic cancer, some experts propose using ultrasonography or MRI/magnetic retrograde cholangiopancreatography to test for pancreatic cancer. However, it is yet unknown whether pancreatic cancer screening and early detection lessen the overall risk of pancreatic cancer death.
All of these screening methods have potential drawbacks as well as advantages. In comparison to mammography, MRI is more prone to produce false-positive results. Furthermore, because they already have a deficit in DNA repair, women with a deleterious BRCA variation may be particularly vulnerable to the DNA-damaging effects of radiation-based diagnostics (such as mammography).
Risk-reducing surgery: Risk-reduction surgery, often known as preventive surgery, entails removing as much “at-risk” tissue as feasible. To lower their risk of BRCA or breast cancer, women may choose to have both breasts removed (bilateral risk-reducing mastectomy). Ovarian cancer risk can reduce the removal of a woman’s ovaries and fallopian tubes (bilateral risk-reducing salpingo-oophorectomy). (Because ovarian tumors frequently start in the fallopian tubes, the fallopian tubes must be removed along with the ovaries.) By removing a source of hormones that can feed the formation of some types of breast cancer, removing the ovaries may also minimize the risk of breast cancer in premenopausal women.
These procedures are permanent, and each one has the risk of complications or injury. In premenopausal women, bleeding or infection, anxiety and body image issues (bilateral risk-reducing mastectomy), and early menopause are all examples (bilateral risk-reducing salpingo-oophorectomy).
Because these methods cannot eliminate all at-risk tissue, risk-reducing surgery can not guarantee that cancer will not develop. That’s why these surgeries are referred to as “risk-reducing” rather than “preventive.” Even after risk-reducing surgery, some women have developed breast cancer, ovarian cancer, or primary peritoneal carcinomatosis (a malignancy comparable to ovarian cancer). Nonetheless, the risks associated with these surgical treatments are considerably less.
Several studies found that women who had bilateral salpingo-oophorectomy had a nearly 80% reduction in the risk of ovarian cancer, a 56% reduction in the risk of breast cancer, and a 77% reduction in the chance of it being fatal from any cause throughout the studies’ follow-up periods.
For bearers of BRCA1 and BRCA2 mutations, the reduction in breast and ovarian cancer risk from removing the ovaries and fallopian tubes appear similar.
Chemoprevention: Chemoprevention is the use of medications to lower cancer risk. The FDA has licensed two chemopreventive drugs (tamoxifen [Nolvadex] and raloxifene [Evista]) to reduce the incidence of breast cancer in women at high risk. However, the effect of these drugs in people with harmful BRCA1 or BRCA2 mutations is unclear.
According to findings from three trials, tamoxifen may help reduce the risk of breast cancer in women who possess damaging BRCA2 variations and the risk of cancer in the opposite breast in BRCA1 and BRCA2 variant carriers being diagnosed with breast cancer. The usefulness of raloxifene in BRCA1 and BRCA2 variant carriers has not undergone in-depth tests.
On the other hand, these drugs may be an alternative for women who do not want or cannot have surgery. Menopausal symptoms, blood clots, stroke, increased risk of endometrial cancer (tamoxifen), and allergic reactions are all possible side effects of these medicines (raloxifene).
It’s challenging to determine what might or not work for a patient. So visit University Cancer Centers and book an appointment with a cancer specialist to get BRCA mutation testing and cure.