Li-Fraumeni Syndrome Follow-up

  • Author: Kavita Patel, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Apr 27, 2011
 

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.
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Deterrence/Prevention

  • Prophylactic mastectomy decreases the risk of only one type of cancer in women at high risk for several other potentially deadly malignancies.
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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. 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.
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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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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; Co-Associate Program Director of the Signal Transduction Program Area, Jonsson Comprehensive Cancer Center, California Nanosystems Institute and Molecular Biology Institute, University of California, Los Angeles, David Geffen School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society for Experimental Hematology, 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.

Specialty Editor Board

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 School of Medicine

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.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Timothy P Cripe, MD, PhD  Professor of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center; Clinical Director, Musculoskeletal Tumor Program, Co-Medical Director, Office for Clinical and Translational Research, Cincinnati Children's Hospital Medical Center; Director of Pilot and Collaborative Clinical and Translational Studies Core, Center for Clinical and Translational Science and Training, University of Cincinnati College of Medicine

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.

Samuel Gross, MD  Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; 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  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

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.

References

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