Such a change is called a somatic alteration. The risk for any one woman depends on a number of factors, some of which have not been fully characterized. Like women with breast cancer in general, those with harmful BRCA1 or BRCA2 variants also have an increased risk of developing cancer in the opposite contralateral breast in the years following a breast cancer diagnosis 2. Ovarian cancer: About 1.
In women, these include fallopian tube cancer 5 , 6 and primary peritoneal cancer 7 , both of which start in the same cells as the most common type of ovarian cancer. In addition, certain variants in BRCA1 and BRCA2 can cause subtypes of Fanconi anemia , a rare syndrome that is associated with childhood solid tumors and development of acute myeloid leukemia 15 — The mutations that cause these Fanconi anemia subtypes have a milder effect on protein function than the mutations that cause breast and ovarian cancer.
Children who inherit one of these variants from each parent will develop Fanconi anemia. While the prevalence in the general population is about 0. Other populations, such as Norwegian, Dutch, and Icelandic peoples, also have founder mutations Anyone who is concerned about the possibility that they may have a harmful variant in the BRCA1 or BRCA2 gene should discuss their concerns with their health care provider or a genetic counselor.
However, testing is not currently recommended for the general public. Instead, expert groups recommend that testing be focused on those who have a higher likelihood of carrying a harmful BRCA1 or BRCA2 variant, such as those who have a family history of certain cancers. Testing can be appropriate for both people without cancer as well as people who have been diagnosed with cancer.
If someone knows they have a mutation in one of these genes, they can take steps to reduce their risk or detect cancer early. And if they have cancer, the information about their mutation may be important for selecting treatment.
Before testing is done, a person will usually have a risk assessment , in which they meet with a genetic counselor or other health care provider to review factors such as which of their relatives had cancer, what cancers they had, and at what ages they were diagnosed. If this assessment suggests that someone has an increased risk of carrying a harmful BRCA1 or BRCA2 gene variant, their genetic counselor can discuss the benefits and harms of testing with them and order the appropriate genetic test, if the individual decides to have genetic testing Some people may choose to have genetic testing via direct-to-consumer DTC testing.
Genetic counseling is recommended for those people as well to help them understand the test results and to make sure the most appropriate test was done. People should be aware that DTC tests may not be comprehensive, in that some tests do not test for all of the harmful mutations in the two genes. The United States Preventive Services Task Force recommends risk assessment for women who have a personal or family history of breast , ovarian , fallopian tube , or peritoneal cancer or whose ancestry is associated with having harmful BRCA1 and BRCA2 variants, as well as follow-up genetic counseling as appropriate.
The American Society of Clinical Oncology recommends that all women diagnosed with epithelial ovarian cancer be offered genetic testing for inherited variants in BRCA1 , BRCA2 , and other ovarian cancer susceptibility genes, regardless of the clinical features of their disease or their family history This is because there are no risk-reduction strategies that are specifically meant for children, and children are very unlikely to develop a cancer related to an inherited BRCA variant.
Sometimes people with cancer find out that they have a BRCA1 or BRCA2 mutation when their tumor is tested to see if they are a candidate for treatment with a particular targeted therapy.
Because harmful BRCA variants reported in the tumor may be of somatic or germline origin, someone with such a variant in their tumor should consider having a germline genetic blood test to determine if the variant was inherited.
When a family history suggests the possibility that someone without cancer may have inherited a harmful variant in BRCA1 or BRCA2 , it is best for a family member who has already been diagnosed with cancer to be tested, if such a person is alive and willing to get tested.
If such testing reveals a known harmful variant, then testing the individual for that variant will provide a clear indication of whether they also carry it. If all family members with cancer are deceased or are unwilling or unable to have genetic testing, testing family members who have not been diagnosed with cancer may still be of value and provide good information.
Genetic counselors can often help answer questions about insurance coverage for genetic testing. Some genetic testing companies may offer testing for inherited BRCA1 and BRCA2 variants at no charge to patients who lack insurance and meet specific financial and medical criteria.
Positive result. However, a positive test result cannot tell whether or when the tested individual will develop cancer. A positive test result may also have important implications for family members, including future generations. Negative result. A negative test result can have several meanings, depending on the personal and family medical history of the person who is tested and whether or not a harmful mutation has already been identified in the family.
If a close blood relative of the tested person is known to carry a harmful BRCA1 or BRCA2 variant, a negative test result is clear: it means the tested person did not inherit the harmful variant that is present in the family and cannot pass it to their children. A person with such a test result, called a true negative, has a risk of cancer that is similar to that of someone in the general population.
However, there are other factors besides genetic factors that may increase the risk of cancer, such as radiation exposures at an early age, and those factors should be considered in assessing their risk of cancer. Sometimes, a genetic test finds a change in BRCA1 or BRCA2 that has not been previously associated with cancer and is uncommon in the general population. As more research is conducted and more people are tested for BRCA1 and BRCA2 variants, scientists will learn more about uncertain changes and cancer risk.
Clinicians and scientists are actively working to share information on these mutations so that they can be reclassified as either clearly harmful or clearly not harmful 26 , Until the interpretation of the variant is clarified, management of risk should be based on family history and other risk factors. However, it is important that a person who has a VUS test result regularly obtains updated information from the testing provider in case that VUS is reclassified as a harmful or likely harmful variant.
Testing providers have different policies about notifying a tested person of a change in the interpretation of a VUS test result. Some will contact the tested person directly, whereas others place the responsibility on the tested person to check back in on a regular basis to learn of updates to the interpretation of their VUS test result.
These include enhanced screening , risk-reducing surgery sometimes referred to as prophylactic surgery , and chemoprevention.
Enhanced screening. Some women who test positive for harmful BRCA1 and BRCA2 variants may choose to start breast cancer screening at younger ages, have more frequent screening than is recommended for women with an average risk of breast cancer, or have screening with magnetic resonance imaging MRI in addition to mammography.
No effective ovarian cancer screening methods are known. Some groups recommend transvaginal ultrasound , blood tests for the CA antigen which can be present at higher-than-normal levels in women with ovarian cancer , and clinical examinations for ovarian cancer screening in women with harmful BRCA1 or BRCA2 variants. However, none of these methods appear to detect ovarian tumors at an early enough stage to improve long-term survival Some expert groups recommend that such men undergo regular annual clinical breast exams starting at age 35 However, it is not yet clear whether pancreatic cancer screening and early pancreatic cancer detection reduces the overall risk of dying from a pancreatic cancer.
All of these screening approaches have potential harms as well as possible benefits. For example, MRI is more likely than mammography to result in false-positive findings. And there is some concern that women who have a harmful BRCA variant might be particularly sensitive to the DNA-damaging effects of tests that involve radiation such as mammography because they already have a defect in DNA repair Risk-reducing surgery.
Risk-reducing, or prophylactic, surgery involves removing as much of the "at-risk" tissue as possible. Women may choose to have both breasts removed bilateral risk-reducing mastectomy to reduce their risk of breast cancer. Surgery to remove a woman's ovaries and fallopian tubes bilateral risk-reducing salpingo-oophorectomy can help reduce her risk of ovarian cancer.
Ovarian cancers often originate in the fallopian tubes, so it is essential that they be removed along with the ovaries. Removing the ovaries may also reduce the risk of breast cancer in premenopausal women by eliminating a source of hormones that can fuel the growth of some types of breast cancer. These surgeries are irreversible, and each has potential complications or harms.
These include bleeding or infection, anxiety and concerns about body image bilateral risk-reducing mastectomy , and early menopause in premenopausal women bilateral risk-reducing salpingo-oophorectomy. Risk-reducing surgery does not guarantee that cancer will not develop because not all at-risk tissue can be removed by these procedures. Nevertheless, these surgical procedures greatly reduce risk.
The reduction in breast and ovarian cancer risk from removal of the ovaries and fallopian tubes appears to be similar for carriers of BRCA1 and BRCA2 variants Chemoprevention is the use of medicines to reduce the risk of cancer.
The information and recommendations appearing on this page are appropriate in most instances, but they are not a substitute for medical diagnosis. For specific information concerning your personal medical condition, JAMA suggests that you consult your physician. This page may be photocopied noncommercially by physicians and other health care professionals to share with patients. Back to top Article Information. Access your subscriptions. Access through your institution. Add or change institution.
Free access to newly published articles. Purchase access. Rent article Rent this article from DeepDyve. Access to free article PDF downloads. Save your search. Customize your interests. Lee recommends that primary care doctors refer patients to a genetic counselor, who can help determine if family history and risk factors call for testing. Counselors can administer the test and properly interpret the results when they're in — they take about three weeks.
Genetic tests can be done in a primary-care doctor's office. The physician sends the patient's blood or saliva sample to a commercial laboratory or a research testing facility. DNA from the sample is used to test for mutations. Consumers interested in online testing should make sure that those companies offer telephone counseling and provide clinical-grade testing.
Be cautious, Lee said, of companies that don't offer counseling. Genetic counseling often is covered by insurance, especially if there is a family history of BRCA-related cancers. Genetic testing may sound like a worrisome endurance test, but many people who undergo it believe it's worth it. Pomerantz certainly does. To make an appointment with a Cedars-Sinai genetic counselor, call the scheduling department at
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