Hereditary Cancer
Genetic testing
Overview
Genetic testing involves taking a sample of blood or tissue in order to learn more about a person’s genes. Genetic testing can be used to determine if someone has changes in their genes that make them more likely to be diagnosed with certain diseases such as cancer. Genetic tests that measure likelihood for a disease are called “predictive genetic tests.”
There is a predictive blood test available that can determine if a person carries a mutation in BRCA1 or BRCA2, the most common genes involved in hereditary breast and ovarian cancers. This test does not determine whether a person has cancer or not; it indicates whether a person carries a change in one of these genes.
Genetic testing does not take the place of tests which screen for certain types of cancer. However, genetic test results may affect recommendations about the type of screening and the age to begin screening. The decision to undergo genetic testing is a very personal one, and the benefits depend on your particular circumstances. For this reason, it is important to speak with a specialist in cancer genetics if you are concerned that cancer may run in your family or if you are interested in genetic testing.
BRCA1 and BRCA2 genetic testing
The two genes most commonly associated with hereditary breast and ovarian cancer are called BRCA1 and BRCA2 (for Breast Cancer 1 and Breast Cancer 2 genes). There is a predictive blood test available that can determine if a person carries a mutation in one of these genes. There are several options for the type of BRCA test ordered. Often the first person in a family to have genetic testing will have what is called “full-sequencing” of the BRCA1 and BRCA2 genes, which means the laboratory examines the DNA of both genes to see if there is a known cancer-causing mutation in one of these genes.
If a mutation has already been identified in a family, then often (but not always) a “single-site” test can be ordered to look for the specific mutation that was already identified. In certain populations (for example, people of Eastern European Jewish descent) there are specific BRCA mutations called “founder mutations” that tend to occur more frequently. For members of these populations, it may be possible to use a special test to look for these common mutations. These “single-site” and “founder-mutation” tests are less expensive tests than “full sequencing.” A specialist in cancer genetics can assure that the correct test is ordered.
Insurance will usually cover the cost of genetic testing. See our page on insurance coverage for more information.
In the United States, BRCA results are usually available in three to five weeks. Under certain circumstances—particularly for individuals newly diagnosed with cancer, for whom test results may affect treatment choices—the test can be run more quickly for an additional cost. In some countries, the results of BRCA testing can take significantly longer than five weeks. The results may also take longer if testing is ordered as part of a research study.
Benefits and limitations of genetic testing
BRCA testing can provide important medical information for the person undergoing the testing and for his or her family members. The potential benefits of genetic testing depend in part on the ability to interpret the test results. Some possible benefits of genetic testing for women already diagnosed with cancer include:
- Testing can help women diagnosed with breast cancer make treatment decisions including whether to undergo lumpectomy and radiation or bilateral mastectomy.
- Testing can help women diagnosed with breast cancer understand their risk for a second primary breast cancer or ovarian cancer and make informed risk management decisions.
- Testing can help family members better understand their risk for cancer and increases the likelihood that relatives who have not had cancer receive an informative genetic test result should they choose to be tested.
For people who have not been diagnosed with cancer, the benefits of the genetic test often depend on whether or not a relative with cancer has been tested first. Genetics experts can help determine whether or not genetic testing is appropriate and interpret the results. Some possible benefits of genetic testing for family members who have not been diagnosed with cancer include:
- Testing negative under certain circumstances may mean that the person did not inherit the risk for cancer and that his or her cancer risk is the same as the general population's risk.
- Testing can help women better understand and manage their risk for breast and ovarian cancer.
BRCA testing and hereditary cancer can be complicated, and genetic testing does not always provide a simple "yes" or "no" answer about hereditary cancer risk within a family. There are test results that are considered "uninformative" which do not provide any additional information about cancer risk within a family.
An expert in cancer genetics can help explain these benefits and limitations further and determine whether or not genetic testing is appropriate and likely to give a person further information about his or her cancer risk.
BRCA prevalence
Most cases of cancer are considered “sporadic” and their cause is unknown. (Visit our section on sporadic vs. hereditary cancer for more information on the differences between these two types of cancer.) About 10% of many cancers—including breast and ovarian cancer—are considered hereditary. BRCA mutations can happen in any population, and mutations have been found in families of all ethnicities. People of certain heritages are more likely to carry BRCA mutations, but families of any ethnic background can carry a mutation.
Experts estimate that, in the general population, one in every 300 to 500 people harbors a BRCA mutation. BRCA mutations are more common in people of Eastern European (Ashkenazi) Jewish descent. It is estimated that one in every 40 people of Eastern European Jewish descent (2.5% of this population) carries a BRCA mutation. Members of certain other ethnic groups may also be more likely than those in the general population to carry a BRCA mutation. However, it is important to remember that any family can have a BRCA mutation, regardless of its ethnic background. Various factors—such as the number of people with cancer, their relationship to each other, age of onset of cancer, and types of cancer—affect the likelihood of a BRCA mutation within a family. A specialist in cancer genetics can look at your heritage and family history, and help determine the likelihood that your family has a BRCA mutation.
Test results
There are three possible test results with BRCA testing: a positive test result, a negative test result, or a “variant of uncertain significance.” A positive BRCA test result will indicate that a “deleterious mutation” was found in either the BRCA1 or BRCA2 gene (or, rarely in both genes). This means that a change was found in the gene which is known to increase the risk for cancer. A negative BRCA test result means that no such gene mutation was found. A “variant of uncertain significance” means that a change was found that may or may not increase the risk for cancer.
Genetic testing may have a wide range of effects on people and their families. Sometimes people need additional support from psychologists or other health-care professionals to help them work through the consequences of their test results. Most genetics specialists work with mental-health care professionals who are skilled in helping people cope with genetic test results. Some people find it helpful to speak with other people who have had genetic testing. FORCE has a rich community of members who have had personal experience with genetic counseling, genetic testing and hereditary cancer. For information visit our section on finding support.
It is important to consult a genetics expert to help interpret and explain genetic test results and provide management recommendations.
Positive test results
A woman who tests positive for a BRCA gene mutation has an increased lifetime risk for breast and ovarian cancer and certain other cancers compared to women in the general population. Even with a positive genetic test, the risk for cancer is not 100%; it is possible to have a BRCA mutation and never develop cancer. A specialist in cancer genetics can help estimate the risk for breast and ovarian cancer in a BRCA mutation carrier. A positive BRCA test can affect treatment options for women diagnosed with cancer, and can affect screening options for women who have not had cancer. It is important to have a health care team that is experienced in managing women with hereditary cancer risk. For more information visit our section on risk management options. Some carriers of a BRCA mutation may be able to enroll in research studies to help prevent cancer, detect cancer early, or treat hereditary cancer. For more information visit our page on research studies.
A man who tests positive for a BRCA gene mutation may be at higher risk for male breast cancer, prostate cancer, and other cancers compared to men in the general population. However, it is possible for a man to have a BRCA mutation and never develop cancer. It is important for a man who tests positive for a mutation to have a health care team that is experienced in monitoring men with BRCA mutations.
A positive test in either a man or woman means that other relatives are at risk for carrying a mutation too. BRCA mutations can be passed on from the father or the mother to a son or daughter equally. There is a 50% chance that a parent will pass on a BRCA mutation to each of their children. It is important to discuss with a specialist in cancer genetics who in the family may be at risk, and who should be informed of genetic test results. For more information visit our page on sharing family medical information.
Negative test results
The significance of a negative BRCA test result depends on the individual and family circumstances of the person being tested. In a family in which a BRCA mutation has already been identified, a negative test can mean that the person does not have a higher risk for breast or ovarian cancer than the general population. In a family with a known mutation, screening recommendations are different for someone who tests BRCA negative than for someone who tests positive. However, since cancer is a common disease and since most cancer has no known cause, a negative genetic test does not guarantee that a person won’t develop cancer in his or her lifetime.
Sometimes hereditary breast and ovarian cancers can be caused by changes in genes other than BRCA1 or BRCA2. Mutations in other genes will not show up in a BRCA test. There are tests for some of these other genes. A specialist in cancer genetics can interpret a negative test result and help you determine whether another genetic test may be appropriate for a your family. For more information visit our page on other hereditary cancer syndromes.
Experts believe that there are other genes related to breast and ovarian cancer risk for which tests are not yet available. In families with a hereditary pattern of cancer but no identified mutation, a negative genetic test cannot entirely rule out a hereditary cancer syndrome. Therefore, members of families with no identifiable gene mutation but a hereditary pattern of cancer may still be at higher risk for cancer than people in the general population, even if they test negative for BRCA or other gene mutations. Certain families with a large number of cancers and no identified mutation may qualify to participate in research looking for other genes that might be linked to hereditary cancers. For more information please visit our page on participating in research.
Variant of uncertain significance
Genes tell our bodies which proteins to make. Not all changes in genes are bad. Some gene changes can mean the difference between black hair and blonde hair, or the difference between brown eyes and green eyes. Other gene changes, called mutations, can cause our body to make proteins that don’t work correctly. Some people receive a BRCA test result called a “variant of uncertain significance.” This means that, at the time of testing, the laboratory cannot determine whether the gene change is a “deleterious change,” which increases the risk for cancer, or a variant which does not increase cancer risk. Over time, as more family members are tested for the variant, sometimes the laboratories will determine whether or not these changes are “deleterious” and will “reclassify” the test result. It is important for people who test positive for a variant of uncertain significance to stay in contact with their genetics specialist to learn if their variant has been reclassified to a deleterious or a harmless mutation. There are research studies looking at whether variants are “deleterious” or harmless. For more information visit our page on participating in research. Cancer screening and risk management recommendations for people who test positive for a variant of uncertain significance are usually different than recommendations for people who test negative and for people in the general population.
Uninformative tests
Sometimes variants of uncertain significance results are considered “uninformative tests” because they don’t provide additional information about a person’s cancer risk. Certain negative test results may also be considered uninformative. In families where there is a strong family history of cancer, the preference is to test someone who has had cancer first. In such a family, if there is no cancer survivor to test first, a negative test may be considered uninformative because it may mean any one of three very different things:
- there is a mutation in the family and the person who was tested doesn’t carry that mutation
- the cancer in the family is not hereditary and is instead sporadic cancer
- the cancer in the family is due to a mutation in a different gene or in a gene which has not yet been discovered and for which there is no available test
It is important to consult a genetics expert to help explain uninformative genetic test results and provide screening recommendations for people with an uninformative test result.
Other websites
Genetic
Testing for Breast Cancer Risk
A good introduction from the National Cancer Institute.
In the Family
This documentary film follows the story of previvor Joanna Rudnick and several families affected by hereditary breast and ovarian cancer.
Breast Cancer Legacy DVD, available to purchase
from the FORCE shop.
This DVD, sponsored by the Young Survival Coalition, profiles several families
dealing with hereditary breast cancer and includes interviews with experts in
cancer genetics.
Laurie Stein's Personal Story
Reporter and FORCE member Laurie Stein tells her personal experience with hereditary breast cancer, genetic testing and dealing with the aftermath of learning that she carries a mutation.
Myriad Genetics
Information for consumers and health care providers, including charts of
BRCA prevalence, produced by the laboratory that conducts BRCA 1 and BRCA 2 testing.
Further reading - books
Breakthrough: The Race to Find the Breast Cancer Gene, by Kevin Davies and Michael White
Positive Results
by Joi Morris and Ora Gordon, MD
One part memoir, three parts guidebook, Positive Results explains in a clear and steady manner the myths and realities of “the breast cancer genes.”
Further reading - articles (advanced reading)
A
prospective study on predictive factors linked to the presence of BRCA1 and BRCA2 mutations
in breast cancer patients
Carla C. Wárlám-Rodenhuis, Veronica C.M. Koot, Rob B. van
der Luijt, Hans F.A. Vasen and Margreet G.E.M. Ausems.
European Journal of Cancer . Volume 41,
Issue 10: p. 1409-1415, July 2005.
BRCA1
variants in a family study of African-American and Latina women
Roberta McKean-Cowdin, Heather Spencer Feigelson, Lucy Y. Xia, Celeste
Leigh Pearce, Duncan C. Thomas, Daniel O. Stram and Brian E. Henderson.
Human Genetics. Volume 116, Number 6:
p. 497-506, May, 2005.
Classification
of BRCA1 missense variants of unknown clinical significance
C M Phelan, V api, B Tice, R Favis, E Kwan, F Barany, S Manoukian, P Radice,
R B van der Luijt, B P M van Nesselrooij, G Chenevix-Trench, kConFab, T Caldes,
M de La Hoya, S Lindquist, S V Tavtigian, D Goldgar, Å Borg, S A Narod
and A N A Monteiro.
Journal of Medical Genetics. Volume 42, Number
2: p. 138-146, May 2005.
Racial
differences in the use of BRCA1/2 testing among women with a family history
of breast or ovarian cancer
Katrina Armstrong, MD, MSCE; Ellyn Micco, BA; Amy Carney, BA; Jill Stopfer,
MS; Mary Putt, ScD
Journal of the American Medical Association. Volume 293, Number
14: p. 1729-1736.
Knowledge,
attitudes, and utilization of BRCA1/2 testing among women with early-onset
breast cancer
Peters N, Domcheck SM, Rose A, Polis R, Stopfer J, Armstrong K.
Genetic Testing. Volume 9, Number 1: p. 48-53,
March 2005.
Functional
evaluation and cancer risk assessment of BRCA2 unclassified variants
Kangjian Wu, Shannon R. Hinson, Akihiro Ohashi, Daniel Farrugia, Patricia
Wendt, Sean V. Tavtigian, Amie Deffenbaugh, David Goldgar and Fergus J. Couch.
Cancer Research. Volume 65, Number 2: p.
417-426, January 2005.
Integrated
evaluation of DNA sequence variants of unknown clinical significance: application
to BRCA1 and BRCA2
David E. Goldgar, Douglas F. Easton, Amie M. Deffenbaugh, Alvaro N. A.
Monteiro, Sean V. Tavtigian, Fergus J. Couch, and the Breast Cancer Information
Core (BIC) Steering Committee.
American Journal of Human Genetics. Volume
75, Number 4: p. 535-544, October 2004.
Prevalence
of BRCA1 and BRCA2 germline mutations in young breast cancer patients:
A population-based study
Silvia de Sanjosé, Mélanie Léoné, Victoria
Bérez, Angel Izquierdo, Rebeca Font, Joan M. Brunet, Thierry Louat,
Loreto Vilardell, Joan Borras, Pau Viladiu, F. Xavier Bosch, Gilbert M. Lenoir,
Olga M. Sinilnikova.
International Journal of Cancer. Volume 106, Issue 4: p. 588 - 593,
September 2003.
Psychosocial
redictors of BRCA ounseling and testing Decisions among urban African-American
women
Hayley S. Thompson, Heiddis B. Valdimarsdottir, Chantal Duteau-Buck, Josephine
Guevarra, Dana H. Bovbjerg, Cassandra Richmond-Avellaneda, David Amarel,
Diana Godfrey, Karen Brown and Kenneth Offit. Cancer
Epidemiology Biomarkers & Prevention. Volume 11: p. 1579-1585, December
2002.
What
do ratings of ancer-specific distress mean among women at high risk of
breast and ovarian cancer?
James C. Coyne, Linda Kruus, Melissa Racioppo, Kathleen A. Calzone, Katrina
Armstrong. American Journal of Medical Genetics.
Volume 116A, Issue 3: p. 222-228, September 2002.
Clinical characteristics
of individuals with germline mutations in BRCA1 and BRCA2: Analysis of
10,000 individuals
Thomas S. Frank, Amie M. Deffenbaugh, Julia E. Reid, Mark Hulick, Brian E.
Ward, Beth Lingenfelter, Kathi L. Gumpper, Thomas Scholl, Sean V. Tavtigian,
Dmitry R. Pruss, Gregory C. Critchfield. Journal
of Clinical Oncology. Volume 20, Issue 6: p. 1480-1490, March 2002.