Hereditary Cancer Genetic Test Results

Genetic testing does not always give you clear answers, but genetic counselors are trained to interpret and explain the test results and what they might mean to you and your family.

Genetic testing can have several possible results:

Means that the laboratory for a mutation that this known to affect the function of the gene.

A positive result may:

  • Confirm the diagnosis of a hereditary cancer syndrome
  • Have an increased risk of developing certain cancer(s) in the future
  • May impact medical management recommendations.
  • Be important information for family members to determine if they want genetic testing to learn if they are at increased risk (if they have the mutation) or if they are at general population risk (if they did not inherit the known mutation).
  • For those who have already been diagnosed with cancer, a positive result may influence how the cancer is treated. Some medications are recommended for individuals with certain types of mutations. Knowing about the genetic disorder before treatment begins allows doctors to modify the treatment.
  • A “negative test result” means that the laboratory did not find a mutation in any of the genes analyzed. There are two types of negative results: uninformative negative and true negative.

Uninformative negative:

  • When a person has a strong family history of cancer but the cause of the cancer is unknown (no known mutation in the family), a negative test result is classified as an “uninformative negative” (does not provide useful information) as the underlying cause of the cancer in the family is unknown.
  • Since there has not been a mutation identified in the family that explains the family history of cancer, it cannot be determined whether an individual did not have a mutation because they did not inherit what was causing the cancer in their family OR that their family may not have an identifiable mutation.
  • Genetic testing cannot identify all cancer susceptibility mutations; so the possibility remains that an individual does possess an undetected cancer susceptibility mutation, causing a high risk for cancer.
  • Because of the possibility of an undetectable mutation individuals with an uninformative negative result should still consider following cancer screening recommendations based on their family history
  • If another family member is found to have a cancer susceptibility mutation an uninformative results may be reinterpreted and the individual's cancer risk would be reevaluated.

True Negative

  • This occurs when a cancer susceptibility mutation (positive result) has been found in a family member.
  • In such a case, a negative result can show that the tested family member has not inherited the mutation that was causing the increased risk for cancer in the family.
  • Because the individual does not have the familial mutation they do not have an increased risk of developing cancer.
  • No increased cancer screening would be recommended. Follow general population screening guidelines (ACS)
  • A true negative result does not mean that there is no cancer risk, but rather that the risk is probably the same as the cancer risk in the general population.
  • If genetic testing shows a change that has not been previously associated with cancer in other people, the person’s test result may report “variant of unknown clinical significance,” or VUS.
  • Based on current information it is unknown if this is a normal variation (polymorphism) or a cancer susceptibility mutation.
  • The information does not help in making health care decisions. Cancer screening recommendations would be made based on the family history.
  • Family members are not recommended to have genetic testing for medical management planning.
  • Most variants of uncertain significance are reclassified as normal variation when enough information has been gathered to determine clinical correlation. Since many of the genes included on the Next Generation Sequencing (NGS) panel are relatively newly described genes, we are seeing a significant amount of variants of uncertain significance. This reflects that we have a limited amount of information about these genes. As more and more genetic testing is done, we would expect these variants of uncertain significance will be reclassified.
We do not inherit cancer – we can inherit an increased risk for cancer.