Breast Cancer Genetic Testing, All You Need to Know

Genetic Risk of Breast Cancer

Breast cancer is the most common cancer in women and the primary reason for cancer-related deaths in women worldwide (American Cancer Society).

Although breast cancer is prevalent in women, it can also develop in men.

It is estimated that approximately 5-10% of all breast cancers are hereditary and they are linked to the inherited gene mutations. Then, most women with breast cancer do not have an inherited gene mutation. Inherited breast cancers usually develop in younger age compared with non-inherited cases, and tumors are more likely to grow in both breasts (National Cancer Institute at the National Institutes of Health).

Genetic testing allows people to know if they have a higher risk to develop breast cancer (and ovarian cancer) as a result of an inherited gene mutation.

Breast cancer genetic testing is either a blood test or a saliva test which analyze DNA to identify harmful changes (mutations) in either one of two breast cancer predisposition genes, BRCA1 and BRCA2.

Here, I will provide information on DNA testing for gene mutations that increase breast cancer risk, benefits of DNA testing and who need to do breast cancer genetic testing.

BRCA1 and BRCA2 Genetic Testing

What are BRCA1 and BRCA2?

BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins (Snyder M, 2016). These two proteins help repair damaged DNA and hence have a role in maintaining the stability of genetic material. When there are harmful changes (mutations) in either of these genes, its protein product does not function correctly. Hence, DNA damage might not be repaired properly. Consequently, cells are more likely to develop additional chromosomal changes that can result in cancer.

The DNA  testing analyzing  BRCA1 and BRCA2  genes determines whether you carry an inherited mutation in either of two genes.

Women who have a harmful inherited  BRCA1/BRCA2 gene mutations are at increased risk of developing breast and ovarian cancer compared with the women who do not have these mutations.  Men with certain inherited BRCA1/2 gene mutations also face an increased risk of breast cancer.

A BRCA1 or BRCA2 genes mutation can be inherited from a person’s mother or father. Each child of a parent who carries a mutation in one of these genes has a 50% chance (or 1 chance in 2) of receiving the mutation. The effects of mutations in BRCA1 and BRCA2 genes are seen even when a person’s second copy of the gene is normal (National Cancer Institute at the National Institutes of Health).

How much is an increased risk of developing breast and ovarian cancer with carrying BRCA1 or BRCA2 genes mutation?

People with a BRCA1/BRCA2 gene mutation have a significantly increased risk of breast cancer or ovarian cancer (for women).

Recent studies have shown that over 80% of women with single BRCA1 and BRCA2 inherited mutation will develop breast or ovarian cancer before age 70 (Synder M, 2016).

Do mutations in other genes increase the risk of breast and/or ovarian cancers?

Although mutations in BRCA1 and BRCA2 genes  are known as primary causes of hereditary breast cancer, they still only account for 15%-20% of cases.

Mutations in other genes also can be responsible for inherited cancer but are present at lower incidence.

A current study of women with a family history of breast cancer who had normal BRCA1 and BRCA2 genes showed that 10% of cases had mutations in an additional 42 genes (Synder M, 2016).

Altogether, no potential gene mutations have not been detected in 70% of hereditary breast cancer cases.

Some genetics labs test a panel of genes (another known genes that increase risks, accounting for 10% of cases) along with BRCA1 and BRCA2 genes.

Who should consider breast cancer genetic testing?

Some people might have a higher risk of carrying harmful genetic mutations, and they should be tested-if they have:

  • A personal history of breast cancer diagnosed at a young age (before age 50 years)
  • A personal history of breast cancer affecting both breasts
  • A personal history of ovarian cancer disease
  • Both breast and ovarian cancers in either the same woman or the same family
  • A history of breast cancer and one or more relatives with breast cancer
  • A male with breast cancer
  • Ashkenazi Jewish ethnicity, with a close relative who has breast, ovarian or pancreatic cancer at any age
  • A family member who has both breast and ovarian cancers
  • A family member with two-sided breast cancer
  • A relative with ovarian cancer
  • A relative with a known BRCA1 or BRCA2 mutation
  • A relative male with breast cancer

Ideally, when an individual has a family history with high genetic risk for breast cancer, it may be most informative first to test a family member who has cancer. If that person has a harmful mutation, then other family members may want to learn more about their probable risks and whether genetic testing might be applicable for them.

Professionals do not recommend that children under age 18, even those with a family history, undergo genetic testing. This is because there are no risk-reduction strategies for children, and children’s risks of developing cancer associated with a BRCA1 or BRCA2 mutation are extremely low.

If you would like to have more information, please visit the Mayo Clinic website and the National Cancer Institute at the National Institutes of Health website.

What do BRCA1 or BRCA2 genetic test results mean?

The results of genetic testing are complicated, and they should be interpreted by experienced doctors and genetic counselors.

In any case, there are three likely results:

Negative result:

What a negative test result means depends on family history and whether a mutation in either one of BRCA1 and BRCA2 genes have been detected in a family member:

True negative: if a close relative of the tested person is known to carry a harmful BRCA1 or BRCA2 gene mutation, a negative test result means: the tested person does not carry the harmful mutation which is the cause of their family’s cancer risk. Hence, This is called a true negative.

Unclear negative: If genetic testing has not already identified any mutation in close relatives with breast or ovarian cancer in the family, a negative test result is less clear. It is possible that a person has a causative mutation in a gene other than BRCA1 or BRCA2 genes that increases cancer risk (among the other 42 genes that account for 10% of inherited cancers), but they are not tested.  Moreover, BRCA1 and BRCA2 mutations are not always inherited; sometimes they occur spontaneously, that is called somatic mutations, and therefore, may not be found in the blood or saliva sample used for genetic testing because they are not present in every cell of the body.  Furthermore, genetic causes of 70% of familial cancers are not still known. Lastly, it is also probable that genetic testing has missed the harmful mutation in BRCA1 or BRCA2 genes.

Positive result:

The test detected a gene mutation that is linked to breast cancer. It means that a person has a significantly increased risk to develop breast or ovarian cancer. However, a positive result doesn’t mean that person eventually develop cancer.  Studies show that over 80% of women with single BRCA1 and BRCA2 mutation will develop breast or ovarian cancer before age 70.

A variant of uncertain significance:

Genetic testing detects a change in either one of the BRCA1/2 genes, but it may not be possible to confirm whether the mutation is harmful. It may or may not be associated with an increased risk of breast and ovarian cancer.

What are the benefits of genetic testing for assessing breast and ovarian cancer risk?

Once a harmful mutation is detected, depending on the mutation, surveillance (increased screening), medications and predictive surgical options are available for reducing the risk of cancer.

You can find further information about options for a positive test result in the Mayo Clinic website.

Lastly, genetic information may be useful in tailoring cancer treatment. Because every tumor is different, cancers of the same tissue (breast or ovarian) may look and behave very differently depending on which mutations are present and which genes are expressed.


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