BRCA Testing

Early Detection Saves Lives

BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are two 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 functioning normally, these genes do not pose any risk to a one’s health. However, some people may be born with or experience mutations of the BRCA genes through their lifetime. Though researchers are still uncertain what causes changes in these genes to occur, people who have BRCA mutations are at increased risk for developing breast cancer compared with people who do not have these mutations. These mutations affect the normal function, thereby potentially allowing cell growth to occur uncontrolled. This test detects mutations in these genes that are linked mainly with hereditary breast and ovarian cancers.

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

  • BRCA1 Mutation
    • Average 65% lifetime risk for breast cancer
    • 40-60% lifetime risk for second breast cancer (not reappearance of first tumor)
    • Average 39% lifetime risk for ovarian cancer
    • Increased risk for other cancer types, such as prostate cancer
  • BRCA2 Mutation
    • Average 45% lifetime risk for breast cancer (in females)
    • 6% lifetime risk for breast cancer (in males)
    • Average 11% lifetime risk for ovarian cancer
    • Increased risk for other cancer types, such as pancreatic, prostate, laryngeal, stomach cancer, and melanoma
BRCA Testing

Causes Of Hereditary Breast Ovarian Cancer (HBOC) Syndrome

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.

In 1996, the American Society of Clinical Oncology recommended that only people with a strong family history of breast cancer or those who have developed breast cancer at an early age may be eligible for BRCA genetic testing and most doctors still adhere to this recommendation today. Candidates for BRCA testing include those with:

  • Breast cancer in two or more close relatives, such as a mother and two sister
  • Early onset of breast cancer in family members, often before age 50
  • History of breast cancer in more than one generation
  • Cancer in both breasts in one or more family members
  • Frequent occurrence of ovarian cancer
  • One or more BRCA positive relatives

Though many women who have already developed breast cancer do not see the need to be tested for BRCA mutations, benefits of knowing may include: better response to treatment designed for BRCA-positive women and helping other family members to take preventive measures against breast cancer.

BRCA1 and BRCA2 are not the only genes that predispose you for breast cancer. Genetic counseling can help determine if testing for additional genes is appropriate and, if so, which of the many options for multi-gene panels is most appropriate for you.

This is not a test for cancer, it is a test that can tell you if a higher risk for breast and ovarian cancer runs in your family based on these certain genes. BRCA Analysis results help women make more informed healthcare decisions  before cancer has a chance to develop, so Be Ready Against Cancer.

BRCA Testing

Pre Test Counselling

A Pre test counselling is a process to give informed consent for genetic testing.

Discussion includes:

  • genetic information relevant to testing
  • benefits and limitations of genetic testing, including potential insurance implications
  • possible test results and what they mean
  • possible outcome of results including implications to healthcare of family members
  • psychosocial issues and anticipated reaction to results 
  • previous and current mental health history, and emotional support during and after genetic testing 
  • sharing information with family members 
  • reproductive options, if relevant. 

Talk with the DNA Xpert Genetic Counselor to schedule a counselling session.

Circumstances in which testing is not indicated

Genetic testing is not generally indicated outside these guidelines although needs to be considered on an individual basis.

Where the most appropriate person in the family has been tested and no mutation found, further BRCA testing is usually not required in the family.

Predictive testing should never be ordered when only an unclassified variant or polymorphism has been identified in a family.

The Genetic Testing Process

For most genetic tests, either a saliva sample or blood sample is collected. This test includes next-generation sequencing and multiplex ligation-dependent probe amplification to evaluate for mutations and large deletions/duplications in the BRCA1 and BRCA2 genes. Results are generally available in two to four weeks.  If your result is positive for a mutation, your doctor will discuss cancer surveillance strategies with you, and possibly recommend testing for other family members.