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Home > Learn > Breast and Ovarian Cancer > Considering Genetic Testing For Breast and Ovarian Cancer
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Breast and Ovarian Cancer
  Considering Genetic Testing

By Kathleen Fergus, MS, CGC

Reviewed by Andrea Fishbach, MS, MPH




Knowing that you have inherited a mutation in BRCA1 or BRCA2 – the two most common genes known to be associated with breast and ovarian cancer – provides valuable information that can help you reduce your risk for these diseases, or catch them early enough to allow successful treatment. Genetic testing for mutations in these genes is complex because there are hundreds of possible mutations to look for. Also, even if a mutation is found it does not mean that a person will certainly develop breast cancer – only that they have a higher risk of the disease.

 
 
 

Complexities of Testing the BRCA1 and BRCA2 Genes

In the world of DNA testing, it's ideal to have a relatively small gene that can contain a limited number of mutations associated with a single disease. In other words, the smaller the area to be analyzed and the fewer mutations to be identified, the easier the testing process. Unfortunately, the two genes known to predispose to breast and ovarian cancer—BRCA 1 and BRCA2 — meet neither of these criteria.

BRCA1 and BRCA2 each contain more than 80,000 base pairs, making them eight times larger than the average gene. Furthermore, there are more than 600 identified mutations in each of these genes that can increase a person's risk for breast cancer. Many of these mutations are unique, meaning they've only been identified in individual families. The exception to this is a handful of breast and ovarian cancer-associated mutations that researchers believe are caused by the founder effect: These distinct mutations are common in populations that historically were relatively isolated or homogenous such as people of Ashkenazi Jewish descent or in people living in Iceland, Denmark, or the Netherlands.

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Who Should Consider Getting a DNA Test?

DNA testing of the BRCA1 and BRCA2 genes is limited to women who are at increased risk for developing hereditary breast and ovarian cancer based on their personal and/or family history.
Physicians and scientists do not consider BRCA1 and BRCA2 genetic testing appropriate for the general population of low-risk individuals. Primarily this is because only 5 percent to 10 percent of all breast and ovarian cancers are caused by mutations in the BRCA1 and BRCA2 genes. In addition, not all women who test positive for one of the known mutations will develop cancer, nor is there a 100 percent effective means of preventing either breast or ovarian cancer once a mutation is discovered.

However, for women who appear to be at high risk for hereditary breast or ovarian cancer based on their personal and/or family history, genetic testing can yield important information. If, for example, such women test positive for a mutation, there are a numbers of options she can pursue to lower her risk for the disease. These options include more aggressive screening guidelines, taking preventive medications, having prophylactic surgery, or altering lifestyles to reduce risk. If, on the other hand, a woman tests negative for a mutation that is known to run in their family, she can have the relief of knowing that she is at no greater risk of developing breast or ovarian cancer than are members of the population at large and thus does not need to follow more aggressive screening and prevention guidelines. However, for people who do not have a known mutation in their family, but still have a strong history of breast or ovarian cancer, genetic testing can yield less conclusive results. If doctors find no mutation in the family, these women must still follow aggressive screening strategies because of their family history of the disease.

If you meet any of the following conditions, you should meet with a genetic counselor to determine whether genetic testing is an appropriate step for you:

  • Have a close relative (parents, grandparents, children, grandchildren) with a known mutation in BRCA1 or BRCA2

  • Have close relatives across more than one generation (for example, a mother and a sister) that have been diagnosed with early-onset (before age 50) breast and/or ovarian cancer

  • Have an individual family member who was diagnosed with both breast and ovarian cancer

  • Have had cancer in both breasts, especially if one or both cancers were discovered prior to age 50

  • Are of Ashkenazi Jewish heritage with breast cancer before age 50 or ovarian cancer at any age

  • Have a male family member with breast cancer

  • Have other associated cancers/conditions

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Where Testing Should Begin?

Even if you meet the above criteria, and are thus at high risk for breast or ovarian cancer, you might not be your family's best candidate for genetic testing. This is because testing should begin with the family member who is most likely to have a mutation — and that generally means someone who's already been diagnosed with breast or ovarian cancer. In this person a testing lab will sequence the entire BRCA1 and BRCA2 gene to look for a mutation. If the lab finds a mutation in that person, the explanation of your family's hereditary cancer is known and other family members can be tested for the same mutation. This makes subsequent testing much easier because physicians will be looking for one specific mutation rather than sequencing the entire genes.

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Available Tests

If you decide to get a genetic test for breast or ovarian cancer, a specialist in this area (such as a genetic counselor or a trained nurse or physician) can review the risks, benefits and limitations of the testing. A sample of blood will be taken, which will be sent to a specific lab (along with confidential information about your family's medical history) for analysis via one of the following three methods:

  • DNA sequencing. As the most comprehensive method of testing the BRCA1 and BRCA2 genes, DNA sequencing usually serves as the starting point for testing in families who have a strong history of breast and/or ovarian cancers but have not yet undergone genetic testing. Because this type of test detects all changes in a gene — regardless of whether such changes affect the gene's function or the protein it produces — it can sometimes produce ambiguous or uninterpretable results (for example, detecting harmless variations in the genetic code, or genetic changes whose link to breast cancer is not known). Also, even though DNA sequencing represents the most comprehensive form of testing, researchers estimate that it still overlooks 5 to 15 percent of the mutations that can occur within these two genes. For this reason, you may still carry a mutation in BRCA1 or BRCA2 even if sequencing doesn't detect a mutation.


  • Multisite analysis. This test looks for the three mutations — called 185delAG, 538insC, and 6174delT — that researchers believe account for 90 percent of the inherited breast and ovarian cancers in people of Eastern European Ashkenazi Jewish descent. Because this test is so specific — that is, it's only designed to detect these three mutations — there's no possibility of an ambiguous or uninterpretable result. The test either turns up one of these mutations (a positive result), or it does not (a negative result). However, a negative test result does not necessarily mean that you do not have a mutation BRCA1 or BRCA2, it simply means that you do not have one of these three particular mutations. For this reason, some people who get a negative result with multisite analysis will decide to have DNA sequencing to identify any mutations in other locations on the BRCA1 or BRCA2 genes. If neither test turns up a mutation, but you have a family history of the disease, then the mutation in your family may be one that cannot be detected or may be in an unidentified susceptibility gene.


  • Single-site analysis. This type of genetic test can only be performed on individuals who come from families in which one member has already tested positive for a mutation in the BRCA1 or BRCA2 gene. Because the cancer-causing mutation has already been identified, researchers only need to look for the one specific mutation. Like multisite analysis, this type of testing is specific enough that there's no possibility of an ambiguous or uninterpretable result. Either you do or you do not carry the mutation that runs in your family.
Test Cost Time Required to Get Results
DNA Sequencing $2,500 3-4 weeks
Multi-site analysis $250-500 1-4 weeks
Single-site analysis $300 1-4 weeks

The Final Decision: To Test or Not to Test?

There are many factors to weigh — some scientific, some emotional — when deciding whether or not to get a genetic test. Ultimately, the decision is a personal one, and no one can tell you with absolute certainty which choice is right for you. What genetics professionals and physicians can do is walk you through the process of testing and make you aware of the relevant issues involved so that you can make the best choice for yourself and your family. (For recent news about the long-term emotional effects of genetic testing, see Related News below.)

 

Related News
In order to view these articles you will need to have a MyGeneticHealth account. If you are not already a member, selecting the article will automatically take you to a page where you can sign up.
Many women have unrealistic expectations about genetic test for breast cancer
Psychological support often wanted after testing for BRCA1/BRCA2 mutation
Genetic testing for breast cancer may have long-term stress effects

References

Neuhausen, S. L. and Ostrander, E.A. (1997). Mutation testing of early-onset breast cancer genes BRCA1 and BRCA2. Genet Test 1(2): 75-83.

Shattuck-Eidens, D., A. et al. (1997). BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing [see comments]. JAMA 278(15): 1242-50.

Ganguly, A. et al. (1997). Genetic testing for breast cancer susceptibility: frequency of BRCA1 and BRCA2 mutations. Genet Test 1(2): 85-90.

Myriad (2000). Multisite analysis of three founder mutations in Ashkenazi population accounts for 90% of inherited mutations in this population. K.Fergus. San Francisco, Myriad

Roa, B.B. et al. (1996). Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet. 14:188-90.

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