Long After Genetic Testing for Hereditary Cancer Risk, Should Some Consider Screening Again?

June 3, 2020 by Tiffani DeMarco

Genetic Testing

By Tiffani A. DeMarco, M.S., CGC

Genetic counseling and testing for hereditary cancer risk have been integral to patient care for many years. The purpose of this process is to provide information to patients regarding their risk of developing certain types of cancers and to guide recommendations for screening and prevention. Genetic testing can also provide patients with information that can be shared with their family members to determine if they may also have an increased risk of developing cancer.

Because this kind of testing has been available since the 1990s and our ability to more broadly screen and interpret the results has evolved extensively since then, patients who underwent genetic testing many years ago may wonder if it’s a good idea to be tested again., One of today’s sophisticated tests may therefore be in order, particularly for those who previously screened negative for cancer predisposition genes or whose testing looked at a limited number of genes.

Why Genetic Testing?

Some general features that are suggestive of hereditary cancer risk include individuals with the following:

  • early onset cancer, often prior to age 50;
  • multiple primary cancers;
  • Ashkenazi Jewish ancestry with a personal and/or family history of breast, ovarian, prostate and/or pancreatic cancer;
  • the same or related cancers in two or more close family members

Genetic testing is typically most informative in a family if it begins with a relative who has a personal history of cancer that is suggestive of hereditary risk. As this is not always possible, genetic testing may still be warranted for an individual who has not had cancer, but who has a significant family history.

Historically, genetic testing for cancer risk was focused on testing for only a few high-risk genes associated with specific types of cancer. More recent advances in technology allow patients to now undergo genetic testing using what is known as multi-gene panel testing. This type of testing provides for the analysis of many genes at one time using a single blood or saliva sample. As there may be many different genes that can cause the same or a related type of cancer, multi-gene panel testing is often an efficient testing option. This testing typically looks for mutations in both high- and moderate-risk genes that can increase the risk for developing cancer. The testing may also include genes associated with several different types of cancer, which may be particularly useful for a patient with a more extensive personal and/or family history of cancer or for those who may have limited information regarding their family’s cancer history.

Who Should Consider Additional Genetic Testing

Patients may have previously undergone genetic testing for hereditary breast and ovarian cancer, which was limited to the high-risk genes known as BRCA1 and BRCA2; or, they may have had testing for hereditary colon cancer, which was limited to the genes associated with Lynch syndrome. If this previous genetic testing was negative, it is often reasonable for these patients to now consider more comprehensive genetic testing using a multi-gene panel. If the results from a multi-gene panel test are positive, indicating a genetic mutation that is known to cause an increased risk for developing cancer, this can provide a patient and their family members with updated information about their cancer risks and medical management recommendations.

If the results from panel testing are negative, meaning that the testing did not identify a mutation in any of the genes on the test, this result should be interpreted in the context of a patient’s personal and family history of cancer, and increased cancer screening may still be recommended.  Another possible result is a variant of uncertain significance, which means that the testing has found a change in one or more of the genes on the test, but it is not clear whether this change causes an increased risk of cancer. The majority of uncertain variants will eventually be reclassified as benign as scientific data about those genetic mutations shed light on their meaning.

If a patient has previously tested positive for a mutation in BRCA1 or BRCA2, for example, it is less likely that they would now test positive for a mutation in another breast cancer gene that would significantly change their screening and/or prevention recommendations. However, it may still be worthwhile for a patient in this situation to discuss prior genetic test results and personal and family history with a genetic counselor to determine if updated testing via a multi-gene panel may be warranted.

It is important to understand that our knowledge about the cancer risks and screening recommendations for many of the genes tested as part of multi-gene panels will continue to evolve and change. The results from multi-gene panel testing can be complex, with significant implications for patients and their family members. Therefore, we recommend that all patients should review their personal and family history with their physicians and also ask for a referral to a genetic counselor to discuss prior genetic testing results and the possible recommendation for additional testing with a multi-gene panel.

Tiffani A. DeMarco, M.S., CGC, is a certified, licensed genetic counselor and director of the cancer genetics program at Inova Schar Cancer Institute in Fairfax, Virginia.


Side Note: Can My Genetic Test Results be Used Against Me?

The Genetic Information Nondiscrimination Act of 2008 (GINA) prohibits employers and/or health insurers from using genetic information, including family history and genetic test results, to discriminate against patients. For certain groups of patients there may be other laws or policies that provide protections that may be similar to GINA. However, GINA does not protect patients from discrimination by life, disability or long-term care insurance companies.

For more information, visit GINAHelp.org. — Tiffani A. DeMarco, M.S., CGC