Li-Fraumeni Syndrome Follow-up

Updated: Mar 02, 2016
  • Author: ; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Follow-up

Further Outpatient Care

Improvements in the treatment of childhood cancers, including acute lymphocytic leukemia, soft-tissue sarcomas, and osteosarcomas, have led to long-term survival in most children diagnosed with these cancers. Potential late effects for the survivors include second primary malignancies. These may occur, in part, because of the carcinogenic effects of chemotherapy and radiation therapy; however, they may also be due to genetic predispositions such as constitutional TP53 mutations.

Clinical evaluation of family members who are potentially affected by Li-Fraumeni syndrome (LFS) should be considered. Although some sources have recommended frequent laboratory and radiographic monitoring of children in Li-Fraumeni syndrome kindreds, no evidence has been established that screening tests significantly improve survival rates in other nonaffected family members.

Factors that complicate the counseling of patients regarding tumor risk and preventative measures include the wide variety of cancer types that can occur, the lifetime cancer risk, and an incomplete understanding of the variability of penetrance.

Prediction of cancer risk is feasible via carrier testing in Li-Fraumeni syndrome kindreds in whom specific constitutional TP53 mutations are documented.

A major issue in Li-Fraumeni syndrome is whether to test children, especially when the child has not been affected. Whether testing should be done, whether the child should be informed of the results, how to talk to children about inherited predisposition to cancer, and what surveillance should be implemented are areas of concern. The medical and psychological risks and benefits to the child need to be carefully considered. [20]

Known affected individuals, either because of a history of a previous cancer consistent with Li-Fraumeni syndrome or because they carry a TP53 mutation, should be advised regarding the following:

  • The potential risk of the wide variety of related cancers and the screening necessary
  • The importance of having an established physician or other healthcare professional who is cognizant of the syndrome involved in ongoing care
  • The potential for genetic testing to evaluate potential risk for family members

Individuals who are at risk based on Li-Fraumeni syndrome family history but who have not had cancer and for whom no TP53 mutation information is available should be closely monitored and offered TP53 testing.

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Deterrence/Prevention

Prophylactic mastectomy decreases the risk of breast cancer in women with Li-Fraumeni syndrome, but it does not decrease the risk for other malignancies. See Imaging Studies for other surveillance methods and strategies.

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Prognosis

Children in families with Li-Fraumeni syndrome who survive an initial cancer have a relative risk of developing a second cancer that is 83 times greater than that of the general population. The risk for a second cancer increases with younger age at diagnosis of the first cancer.

A second cancer generally occurs 6-12 years after the first cancer. The cumulative probability of a person affected by Li-Fraumeni syndrome developing a second cancer is 57% at 30 years after developing the first cancer. [8]

The risk for a second cancer increases with radiation exposure. Patients with Li-Fraumeni syndrome have a predilection for developing subsequent primary tumors (especially sarcomas) in prior radiation fields.

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Patient Education

Genetic counseling for at-risk individuals in families with Li-Fraumeni syndrome is important to provide the necessary information to allow decision making regarding TP53 testing, if it is feasible, and to discuss the need for close medical follow-up care.

Individuals affected by Li-Fraumeni syndrome who are successfully treated for cancer must understand the significant risk of developing further primary malignancies and the need for close medical follow-up care.

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