eMedicine Specialties > Pediatrics: General Medicine > Oncology

Li-Fraumeni Syndrome: Follow-up

Author: Kavita Patel, MD, Clinical Postdoctoral Fellow in Pediatric Hematology and Oncology, Department of Pediatrics, Baylor College of Medicine
Coauthor(s): Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA; Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Contributor Information and Disclosures

Updated: Dec 1, 2008

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 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) is controversial. Although some sources have recommended yearly CBC counts and abdominal ultrasonography in children in Li-Fraumeni syndrome kindreds, no evidence has been established that these or other screening tests significantly improve the ability to diagnose cancer or increase survival rates.
    • 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. Due to ethical considerations, some medical genetics laboratories do not perform testing for TP53 mutations nor do they report TP53 mutations in clinically unaffected minors in families with Li-Fraumeni syndrome. Closely monitor known carriers of TP53 mutations.
    • Individuals who are known to be affected, 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: (1) the potential risk of the wide variety of related cancers, (2) the importance of having an established physician or other health care professional who is cognizant of the syndrome involved in ongoing care, and (3) 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, similar to those with known predilection.

Deterrence/Prevention

  • Prophylactic mastectomy decreases the risk of only one type of cancer in women at high risk for several other potentially deadly malignancies.

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. Patients with Li-Fraumeni syndrome have a predilection for developing subsequent primary tumors (especially sarcomas) in prior radiation fields.
  • Cumulative probability of a person affected by Li-Fraumeni syndrome developing a second cancer is 57% at 30 years after developing the first cancer.

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.

Miscellaneous

Medicolegal Pitfalls

  • Obtaining a thorough family history with particular emphasis on cancer can be tedious but is an important part of the evaluation of every child diagnosed with a malignancy. Families in which predisposition for cancers is evident should have access to genetic counseling to help provide them with appropriate assessment of risk, delineation of possible interventions or behaviors that can affect risk, and assistance in dealing with the emotional stress associated with the potential of developing cancer.
  • Testing for germline TP53 mutations is available, but considerations should be made regarding its use. Use of this test a general screening evaluation in patients with cancer is very limited; however, patients and families with histories consistent with Li-Fraumeni syndrome (LFS) or with presentations of cancer suggestive of a possible germline TP53 mutation should be counseled regarding the accessibility of testing.
    • Initially, testing should be limited to an affected individual (ie, in whom cancer has been diagnosed) to determine if a TP53 mutation is present. Then, subsequent testing of at-risk family members can be limited to the specific mutation previously documented. Most clinical laboratories do not test family members who are minors if they do not have cancer.
    • Prior to testing, ensure that the significance of either a positive or negative result is clear to all patients and relatives. Explain that no simple screening or intervention exists that can eliminate the potential of developing cancer for those who carry the mutation.
  • Family members whose test results are negative for the TP53 mutation but for whom the mutation was previously established in an affected relative can be reasonably reassured of a low risk of developing cancer at an early age. However, they should understand that this does not mean they are immune to developing a malignancy at some point. Generally, cancer is a multifactorial condition, and risk may depend on health-related behaviors (eg, cigarette smoking, diet) and other potential genetic factors.
  • Patients in families with Li-Fraumeni syndrome who are treated for cancer must be counseled regarding the significant risk of developing other primary malignancies and appropriate follow-up monitoring.
 


More on Li-Fraumeni Syndrome

Overview: Li-Fraumeni Syndrome
Differential Diagnoses & Workup: Li-Fraumeni Syndrome
Treatment & Medication: Li-Fraumeni Syndrome
Follow-up: Li-Fraumeni Syndrome
References
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References

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Further Reading

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Keywords

Li-Fraumeni syndrome, LFS, LFL kindred, p53 mutation, Li-Fraumeni–like kindred, germline mutation, p53 tumor suppressor gene mutation, TP53, TP53 tumor suppressor gene mutation, breast cancer, brain tumor, acute leukemia, soft tissue sarcoma, osteosarcoma, adrenal cortical carcinoma, sarcoma, Ewing sarcoma

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Contributor Information and Disclosures

Author

Kavita Patel, MD, Clinical Postdoctoral Fellow in Pediatric Hematology and Oncology, Department of Pediatrics, Baylor College of Medicine
Kavita Patel, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, Phi Beta Kappa, and Texas Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania
Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Timothy P Cripe, MD, PhD, Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center
Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Executive Director, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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