Li-Fraumeni Syndrome

Who should undergo genetic testing for LFS?

You should consider genetic testing if you or your family members meet one or more of the following criteria:
1. Sarcoma diagnosed before the age of 45
2. Sarcoma diagnosed at any age, with a relative diagnosed with cancer before the age of 45 or a sarcoma diagnosed at any age
3. Breast cancer diagnosed before the age of 31
4. A LFS-related condition* diagnosed before the age of 46 and a family history of cancer
5. Two or more LFS-related conditions* in the same individual
6. Two or more family members on the same side of the family with a LFS-related condition* before the age of 56
7. Adrenocortical cancer or rhabdomyosarcoma at any age
8. Tumour in the choroid plexus (membrane surrounding the brain) at any age
9. A previously identified faulty TP53 gene in the family
10. A TP53 gene fault identified at high frequency on tumour testing

While LFS may run in families, up to 25% of individuals with LFS may have acquired a faulty TP53 gene at birth (de novo). Therefore, genetic testing may also be offered in the absence of relevant family history and/or if an individual’s personal history is suspicious for LFS.

*LFS-related conditions:

• Soft tissue cancer (sarcoma)
• Bone cancer (osteosarcoma)
• Central nervous system tumour
• Breast cancer (often early-onset)
• Adrenocortical tumour
  
• Leukaemia
• Bronchoalveolar cancer
• Colorectal cancer

How can your genetic test result help you?

1. Personalised management
   Your genetic test result may confirm whether your personal and/or family history is due to a hereditary condition like LFS, and clarify what your lifetime cancer risks may be. This information can be useful for doctors to personalise your medical care to help manage or reduce cancer risks.

    

   If you have a cancer diagnosis

   • Helps guide important treatment and/or surgical decisions
   • Indicates what other cancers you are at risk of and how to manage these risks

    

   If you are currently cancer-free

   • Helps guide management and relevant screening options for you to detect cancer at its earliest, most treatable stage
   • Helps guide your lifestyle and screening decisions (e.g., unnecessary radiation exposure should be avoided)
     
   • Helps guide decisions regarding relevant cancer risk-reducing interventions (e.g., surgery)
   • Allows individuals with LFS to consider dedicated reproductive options for family planning

    

2. Familial implications
   Your genetic test result can also help you understand if other family members are at risk of LFS. They can subsequently consider their own testing (predictive testing) to clarify their carrier status to determine tumour and cancer risks.
   
   Family members who have inherited the same faulty TP53 gene may be at increased risk of tumours and cancer and can benefit from management options such as screening (to detect tumours and cancer at an early and manageable stage) or surgery (to reduce their risk of cancer).
   
   Family members who did not inherit the faulty TP53 gene can avoid unnecessary screening and worry. Their children will also not be at risk.