Study: Mutations found through multigene panel testing for cancer risk can change patient care

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This study is about:

Whether or not mutations in cancer risk genes that are found through multigene panel testing might change cancer risk management decisions of people who have a personal and/or family history consistent with hereditary breast and ovarian cancer (HBOC) but do not have mutations in BRCA1/2.

Why is this study important?

Multigene panels can identify up to 50% more patients with mutations in cancer risk genes than testing for BRCA1/2 alone, but will identifying these mutations change care for these patients? Some tests search for low-to-moderate risk genes for which management guidelines are not well established; others test for well-known hereditary cancer syndromes that might require additional screening or risk-reducing surgery, meaning that these findings have clinical utility (or clinical actionability), as physicians use this information to manage cancer risk.

Key study finding(s):

  1. Approximately 4% (40 out of 1,046 study participants) of patients were found to have mutations in genes other than BRCA1/2 that are associated with increased cancer risk.  
  2. About half of patients with mutations in genes other than BRCA1/2 qualified for additional cancer screening or risk management beyond what would be recommended based on their personal and family history alone. 

What does this mean for me?  

This study demonstrates that multigene panel tests can find mutations in genes that increase cancer risk, and that these results can change health care providers’ recommendations for cancer risk management. If you are considering BRCA testing, or you have tested negative for a BRCA mutation in the past, you should discuss with your health care provider whether multigene panel testing is appropriate for you. If this testing is appropriate, it is also important to consult with a genetics expert who can help you understand what different results will mean for you and how they will affect your family. 

This article is relevant for:

People with a personal or family history of cancer where no mutation has been found

This article is also relevant for:

Breast cancer survivors

Women under 45

Women over 45


Be part of XRAY:

Questions to Ask
  • I have a family history of cancer, but am BRCA1/2 negative. Should I be tested for other mutations?
  • Will my insurance company pay for multigene testing?
  • Can you refer me to a genetics expert?
  • I have tested positive for a Variant of Unknown Significance. What should I do?
  • Do you recommend I have testing, and if so, which test?


Study background:

Guidelines are well established for the care of patients with mutations in BRCA1/2 or other genes associated with known hereditary cancer syndromes. However, national patient care guidelines do not exist for many of the low-to-moderate risk cancer genes that may be detected on multigene panel tests (tests that allow healthcare providers to simultaneously search for numerous cancer risk increasing genes).  Mutations in low-to-moderate risk cancer genes increase a person’s risk of cancer, but the risk is lower than risk from mutations in genes associated with known cancer syndromes such as BRCA, PTEN, TP53, CDH1, and genes that are associated with Lynch syndrome.  In the absence of a known mutation associated with increased cancer risk, health care providers typically base screening and prevention recommendations on an individual’s personal and/or family history of cancer.  Just how often these mutigene panel tests yield mutation findings that will change patient care is unknown. 

Researchers of this study wanted to know:

Whether mutations in cancer risk genes identified in patients through multigene panels will change a patient’s recommended care.

Population(s) looked at in the study: 

The 1,046 women involved met national guidelines for hereditary breast and ovarian cancer (HBOC) evaluation through genetic counseling and/or testing based on their personal and/or family history of cancer. Patients with known BRCA1/2 mutations were excluded. For some of the analysis, 23 participants with similar personal and/or family histories who were already known to carry non-BRCA1/2 mutations were included.  Patients were tested using a multigene panel that included either 25 or 29 genes associated with increased cancer risk.

Mutations were found in a variety of genes, including CDH1, TP53, PALB2, MLH1, APC, CHEK2, and ATM.

Study results:

  • 4% (40 out of the 1,046 untested women) of the study participants were found to have mutations other than BRCA1/2 that were associated with increased cancer risk. 
  • Among breast cancer patients in the study, no association was found between age of diagnosis and prevalence of breast cancer-associated genes. This differs from what is seen with BRCA1/2 mutation carriers.
  • Combining the 40 people for whom mutations were detected during the study, and the 23 people who had previously detected mutations before the study, researchers observed that 52% of the total group met national guidelines for additional cancer-specific screening and/or prevention measures that they would not have received if the mutations had not been detected.
    • Almost 33% of these patients had mutations in high-risk genes such as mutations associated with Lynch syndrome that are associated with detailed management guidelines.
    • Family testing would now be recommended for close relatives of 70% of these study participants because their genetic test results would change their cancer risk management.

One limitation of the study is that the author-defined clinical utility will change as more research is conducted on genes that are associated with moderate cancer risk. As more information about different gene mutations comes to light, established national guidelines can be created to better care for patients carrying those mutations. For example, the American Society of Clinical Oncology (ASCO) has recently issued a new policy statement for oncologists on how they should use multigene risk panels. Dr. Noralane Lindor, an author on the newly issued guidelines has said,  "There are some genes on these panels that we know almost nothing about." But, these guidelines have more information than previous guidelines and health care providers and researchers will have even more information for future guidelines.  ASCO recommendations include assuring multigene panel tests are ordered by a provider with expertise in cancer risk assessment.  FORCE supports the position that anyone considering genetic testing speak with a genetics expert before and after testing.


Multigene panel testing for HBOC risk assessment identifies patients with mutations that will change health care provider recommendations for their medical care. This is relevant to people who test negative for a BRCA1/2 mutation but discover they carry other mutations that put them at increased cancer risk. In some cases, mutations are found in genes associated with known hereditary cancer syndromes, such as Lynch syndrome, that have well-defined national guidelines outlining care. In other cases, mutations in some genes included in panel tests do not yet have established guidelines, but as more people with these mutations are identified, we will have additional opportunities to study outcomes.  This information can aid in developing guidelines for people with those mutations. 


Desmond A, Kurian AW, Gabree M, et al. “Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment.” JAMA Oncology, Published first online on August 13, 2015. 

Steenhuysen J. “New Guidelines for cancer doctors aim to make sense of gene tests.” Reuters, August 31, 2015.

Robson, ME, Bradbury, AR, Arun, B, et al. “American Society of Clinical Oncology Policy Statement Update:  Genetic and Genomic Testing for Cancer Susceptibility.” Journal of Clinical Oncology, published first online August 31, 2015.  

posted 9/22/15

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