The information on this page was reviewed and approved by
Maurie Markman, MD, President, Medicine & Science at CTCA.

This page was updated on May 21, 2021.

Li-Fraumeni syndrome

Li-Fraumeni syndrome (LFS) is a hereditary genetic condition that increases the predisposition to cancer. Families whose members have this syndrome face a higher risk of developing cancers across several generations and at younger ages.

The most common types of cancer found in LFS families include osteosarcoma (bone cancer), soft tissue sarcoma, acute leukemia, breast cancer, brain cancer, and adrenal cortical tumors. However, other types have been linked to LFS, including stomach, lung, pancreatic and colon cancers.

What causes LFS?

LFS is most often linked to an alteration in a gene called TP53. (Some families with LFS also have mutations in the gene called CHEK2, but the extent of its association with cancer is unclear.)

TP53 is the genetic blueprint for a protein called p53, which stops tumors from growing. P53 is often referred to as the “guardian of the genome.” When there’s a mutation in TP53, the blueprint is flawed. This, in turn, causes the creation of an imperfect p53 protein.

Generally, every cell in the body has two copies of each gene, one from each parent. A person needs only one mutated copy of the TP53 gene to develop LFS. In fact, most people with LFS have one normal copy of TP53 and one mutated copy, most often passed down from a parent affected by LFS.

However, according to the American Society of Clinical Oncology, 25 percent of LFS patients have no family history of LFS. This means that these patients developed a new, random mutation instead of inheriting a mutated gene.

How is LFS diagnosed?

Classic Li-Fraumeni syndrome is diagnosed if a patient shows a molecular testing mutation in TP53 or meets all three of the points below:

  • A diagnosed sarcoma before age 45
  • A parent, sibling or child (a first-degree relative) who is diagnosed with any type of cancer before age 45
  • A first-degree (parent, sibling or child) or second-degree (grandparent, grandchild, aunt, uncle, niece, nephew, half-sibling) relative diagnosed with any cancer before reaching 45 years old or a sarcoma at any age

LFS may be suspected in a patient who develops early-onset hypodiploid acute lymphoblastic leukemia (ALL) or shows TP53 changes in tumor tissue testing.

Another method is the Chompret Criteria. An LFS diagnosis may be suspected if the patient has a personal and family history that meets one of these four points:

  • A tumor that falls within the LFS spectrum before the patient reaches 46 years old, such as premenopausal breast cancer, soft tissue sarcoma, adrenocortical tumor, central nervous system tumor or osteosarcoma; plus at least one first- or second-degree relative with an LFS tumor before age 56 or multiple tumors (but not breast cancer-related)
  • Multiple tumors other than breast tumors, with at least two of the tumors falling within the LFS tumor spectrum and the first one developing before the patient turned 46 years old
  • An adrenocortical carcinoma or choroid plexus tumor or rhabdomyosarcoma of embryonal anaplastic subtype, regardless of family history
  • Breast cancer before a woman turns 31 years old

From here, testing such as single-gene testing or a multigene panel may be done.

Cancer screening

It’s not possible to correct the mutation in the P53 gene, so attention focuses on rigorous monitoring for signs of cancer, called cancer surveillance. These checks are extremely important for people with LFS (or suspected LFS) because the lifetime cancer risk is ≥70 percent for men and ≥90 percent for women, according to a GeneReviews article.

For many types of cancer, treatment is typically more successful the earlier it’s started. A StatPearls report outlines the important screenings used to look for early signs.

  • Yearly physical exam
  • Prompt evaluations for new or unexplained symptoms
  • Yearly whole-body magnetic resonance imaging (MRI)
  • Ultrasounds (abdominal and pelvic) every three to four months for children and yearly for adults
  • Comprehensive blood testing every four months
  • Breast cancer monitoring, including monthly breast self-examination; twice-yearly breast exams; and yearly breast MRI starting between the ages of 20 and 25
  • Colonoscopy every two to five years, beginning between the ages of 25 and 30, or five years before the age at which the youngest family member developed colon cancer

Treating LFS

A patient’s care team may include a geneticist, an internist, an oncologist and a radiologist—each dedicated to showing the person how best to manage various aspects of care. Psychological health is important, too—people with LFS often deal with anxiety and depression because of the uncertainty surrounding the condition. Patients should ask their doctor, or a therapist or psychiatrist, about emotional assistance.

Regardless of whether a cancer patient has LFS, the treatment options are likely to be the same.