Genetic Testing For Breast And Ovarian Cancer Risk

Learning More, Making Decisions

Genetic testing is a process for determining genetic alterations that may be linked with an increased risk of breast and ovarian cancer.

Genetic testing may reveal whether the cancer risk in a family is passed through its genes.

The National Cancer Institute (NCI) states that there can be benefits to genetic testing, whether a person receives a positive or a negative result.

The potential benefits of a negative result include a sense of relief and elimination of the need for special preventive checkups, tests, or surgeries.

A positive test result can bring relief from uncertainty and allow people to make informed decisions about their future, including taking steps to reduce cancer risk.

In addition, many people are able to participate in medical research that may, in the long run, decrease the risk of death from breast cancer, according to the NCI.

Genetic testing for breast and ovarian cancer risk involves looking for altered genes such as BRCA1 and BRCA2.  Although the lab test is quite complex, only a blood sample is needed.

If a woman is at increased risk for breast or ovarian cancer, she can make choices that may help reduce her risk of getting cancer or help find cancer early.

Cancers develop due to alterations (mutations) in genes. When an alteration or mutation in a gene is present in the eggs and sperm, also called germ cells, it is referred to as a “germline mutation.” When a germline mutation is inherited it is present in all body cells.

Only a small percentage of cancers involve inherited mutations that are passed from generation to generation.

The majority of cancers can be attributed to "acquired" mutations. Acquired means that the mutations occur only in the tissue that is affected by cancer and are not present in all cells of the body. Acquired mutations are not inherited and are not passed down to children.

In fact, all people have altered forms of some genes, according to the NCI. Some alterations can increase risk for certain illnesses such as cancer. In recent years, gene alterations have been found in some families with a history of breast cancer. Some women in these families also have had ovarian cancer.

Hereditary Breast Ovarian Cancer Syndrome

Hereditary breast ovarian cancer (HBOC) syndrome is characterized by the following features in a family:

• an early age of onset of breast cancer (often before age 50)
  
  
• family history of both breast and ovarian cancer
  
  
• increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently) or an individual with both breast and ovarian cancer
  
  
• an autosomal dominant pattern of inheritance (vertical transmission through either the mother or father’s side of the family)
  
  
• an increased incidence of tumors of other specific organs, such as the prostate
  

Other factors that increase the chance that a family has the hereditary breast ovarian cancer syndrome include family history of male breast cancer and Ashkenazi Jewish ancestry.

BRCA1 and BRCA2 Genes

In 1990, DNA linkage studies on large families with the above characteristics identified the first gene associated with breast cancer.

Scientists named this gene “breast cancer 1” or BRCA1 (pronounced brak-uh). BRCA1 is located on chromosome 17.

Mutations in the gene are transmitted in an autosomal dominant pattern (a gene on one of the first 22 pairs of chromosomes, which, when present in one copy, causes a trait or disease to be expressed) in a family.

Since it was clear that not all breast cancer families were linked to BRCA1, studies continued and in 1994, scientists discovered another gene (similar to BRCA1), and named it BRCA2.

BRCA2 is located on chromosome 13. Mutations in this gene are also transmitted in an autosomal dominant pattern in a family.

Both BRCA1 and BRCA2 are tumor suppressor genes that usually have the job of controlling cell growth and cell death. Everyone has two BRCA1 (one on each chromosome #17) and two BRCA2 genes (one on each chromosome #13).

When a person has one altered or mutated copy of either the BRCA1 or BRCA2 gene, their risk for various types of cancer increases.

The following are facts about BRCA1 mutations:

• 36 percent to 85 percent lifetime risk for breast cancer
  
  
• 40 percent to 60 percent lifetime risk for second breast cancer (not reappearance of first tumor)
  
  
• 20 percent to 60 percent lifetime risk for ovarian cancer
  
  
• increased risk for other cancer types, such as prostate cancer 

The following are facts on BRCA2 mutations:

• 36 percent to 85 percent lifetime risk for breast cancer (in females)
  
  
• 6 percent lifetime risk for breast cancer (in males)
  
  
• up to 27 percent lifetime risk for ovarian cancer
  
  
• increased risk for other cancer types, such as pancreatic, prostate, laryngeal, stomach cancer, and melanoma
   

Both copies of a tumor suppressor gene must be altered or mutated before a person will develop cancer.

In HBOC, the first mutation is inherited from either the mother or father and is therefore present in all cells of the body.

This is called a germline mutation. Whether a person who has a germline mutation will develop cancer and where the cancer(s) will develop depends upon where (which cell type) the second mutation occurs.

For example, if the second mutation is in the ovary, then ovarian cancer may develop. If it is in the breast, breast cancer may develop. The process of tumor development actually requires mutations in multiple growth control genes.

Loss of both copies of BRCA1 or BRCA2 is just the first step in the process. What causes these additional mutations to be acquired is unknown. Possible causes include chemical, physical, or biological environmental exposures, or chance errors in cell replication.

Some individuals who have inherited a germline BRCA1 or BRCA2 mutation never develop cancer because they never get the second mutation necessary to knock out the function of the gene and start the process of tumor formation.

This can make the cancer appear to skip generations in a family, when, in reality, the mutation is present. Persons with a mutation, regardless of whether they develop cancer, however, have a 50/50 chance to pass the mutation on to the next generation.

It is also important to remember that the BRCA1 and BRCA2 genes are not located on the sex chromosomes. Therefore, mutations can be inherited from the mother or the father’s side of the family.

Always consult your physician for more information.

Online Resources

American Cancer Society

American Society for Clinical Oncology

Centers for Disease Control and Prevention (CDC)

National Cancer Institute

National Institutes of Health (NIH)

National Women's Health Information Center 

April 2004

Genetic Testing For Breast And Ovarian Cancer Risk

Hereditary Breast Ovarian Cancer Syndrome

BRCA1 and BRCA2 Genes

Statistics for Breast and Ovarian Cancer

Testing Pluses and Minuses

Questions to Ask About Genetic Testing

Online Resources

Other Resources:

St. John's Mercy Cancer Services

Find a St. John's Mercy Physician

Breast Health Information

Women's Health Information

St. John's Mercy Classes and Programs

Statistics for Breast and Ovarian Cancer 

According to estimates of lifetime risk from the National Cancer Institute (NCI), about 13 percent (132 out of 1,000 individuals) of women in the general population will develop breast cancer, compared with estimates of 36 to 85 percent (360 to 850 out of 1,000) of women with an altered BRCA1 or BRCA2 gene.

In other words, women with an altered BRCA1 or BRCA2 gene are three to seven times more likely to develop breast cancer than women without alterations in those genes.

Lifetime risk estimates of ovarian cancer for women in the general population indicate that 1.7 percent (17 out of 1,000) will get ovarian cancer, compared with 16 percent to 60 percent (160 to 600 out of 1,000) of women with altered BRCA1 or BRCA2 genes.

A woman’s lifetime chance of developing breast and/or ovarian cancer is greatly increased if she inherits an altered BRCA1 or BRCA2 gene.

Women with an inherited alteration in one of these genes have an increased risk of developing these cancers at a young age (before menopause), and often have multiple close family members with the disease. These women may also have an increased chance of developing colon cancer.

Men with an altered BRCA1 or BRCA2 gene also have an increased risk of breast cancer (primarily if the alteration is in BRCA2), and possibly prostate cancer.

Testing Pluses and Minuses

The National Cancer Institute (NCI) suggests that genetic testing may help a woman:

• make medical and lifestyle choices
  
  
• find out that the altered gene is not present 
  
  
• cope with a cancer risk
  
  
• decide whether or not to have prophylactic surgery
  
  
• give other family members useful information (if a woman chooses to share test results)
  
  
•  contribute to research
  

There are also disadvantages to testing, according to the NCI:

• there is no proven way to reduce cancer risk
  
  
• there is no guarantee that test results will remain private
  
  
• a woman may face discrimination for health insurance, life insurance, or employment
  
  
• a woman may find it harder to cope with a cancer risk knowing the test results
  
  
• negative test results may provide a false sense of security because a woman thinks she has no chance of getting cancer, which is not true. She would still have the same risk as women in the general population.
  
  
• genetic testing can affect relationships with family members. A woman should think about who in her family might want to know your test results, and whom she might want to tell.
  

A woman will need to decide what the advantages and disadvantages of testing are for her. What is right for one person is not always right for another.

Always consult your physician for more information.

Questions to Ask About Genetic Testing

If a woman is considering genetic testing, she should discuss this with her physician or genetic counselor. The following questions are provided by the National Cancer Institute (NCI):

• What are the chances that a gene alteration is involved in the cancer in my family?
  
  
• What are my chances of having an altered gene?
  
  
• Besides altered BRCA1 or BRCA2 genes, what are other risk factors for breast and ovarian cancer?
  
  
• Are all genetic tests the same?
  
  
• How much does the test cost?
  
  
• How long will it take to get my results?
  
  
• What are the possible results of the test?
  
  
• What would a positive result mean for me?
  
  
• What would a negative result mean for me?
  
  
• How might a positive test result affect my health insurance? life insurance? employment?
  
  
• Do I want to submit my test results to an insurance company? If yes, will they pay for the testing?
  
  
• Where will my test results be placed/recorded? How might this affect me? Who will have access to them?
  
  
• Will having the test do anything to make me change my current health practices?
  
  
• What are my reasons for wanting to be tested?
  
  
• What type of cancer screening would be recommended if I don't get tested?
  

Always consult your physician for more information.