Li-Fraumeni syndrome is diagnosed based on clinical criteria and/or genetic testing for the mutation in the TP53 gene. Genetic testing is typically considered with the below delineated criteria.

Clinical Testing (Clinical Screening & Genetic Testing)

The potential of genetic testing (and the implications of the results) should always involve discussions with a genetic counselor, medical providers, and family.

As delineated by the American Society of Clinical Oncology, the below criteria can be used in determining if genetic testing should be considered:

Classic LFS is diagnosed when a person has all of the following criteria:

  • A sarcoma diagnosed before age 45
  • A first-degree relative, meaning a parent, sibling or child, with any cancer before age 45
  • A first-degree relative or second-degree relative, meaning a grandparent, aunt/uncle, niece/nephew, or grandchild, with any cancer before age 45 or a sarcoma at any age

Chompret Criteria for Clinical Diagnosis of Li-Fraumeni Syndrome has been proposed recently to identify affected families beyond the classic criteria listed above. A diagnosis of LFS and performing TP53 gene mutation testing is considered for anyone with a personal and family history that meets 1 of the following 3 criteria:

Criterion 1

  • A tumor belonging to the LFS tumor spectrum, before the age of 46. This means any of the following diseases: soft-tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumor, adrenal cortical carcinoma, leukemia, or lung cancer, and
  • At least 1 first-degree or second-degree family member with an LFS-related tumor, except breast cancer if the individual has breast cancer before the age of 56 or with multiple tumors

Criterion 2

  • A person with multiple tumors, except multiple breast tumors, 2 of which belong to the LFS tumor spectrum and the first of which occurred before age 46

Criterion 3

  • A person who is diagnosed with adrenocortical carcinoma or a tumor in the choroid plexus, a membrane surrounding the brain, regardless of family history.

Li-Fraumeni-like Syndrome (LFL) is another, similar set of criteria for affected families who do not meet Classic criteria (see above). There are 2 suggested definitions for LFL:

LFL Definition 1, called the Birch definition:

  • A person diagnosed with any childhood cancer, sarcoma, brain tumor, or adrenocortical tumor before age 45 and
  • A first-degree or second-degree relative diagnosed with a typical LFS cancer, such as sarcoma, breast cancer, brain cancer, adrenocortical tumor, or leukemia, at any age and
  • A first-degree or second-degree relative diagnosed with any cancer before age 60

LFL Definition 2, called the Eeles definition:

  • 2 first-degree or second-degree relatives diagnosed with a typical LFS cancer, such as sarcoma, breast cancer, brain cancer, adrenocortical tumor, or leukemia, at any age

Other risk factors to consider, specific to breast cancer:

  • A woman who has a personal history of breast cancer at a younger age and does not have an identifiable mutation in breast cancer genes 1 or 2, called BRCA1 or BRCA2, may have a TP53 mutation.
    • A woman who is diagnosed with breast cancer before age 30 and is not found to have a BRCA mutation has an estimated 4% to 8% likelihood of having a TP53 mutation.
    • Women with breast cancer diagnosed between ages 30 and 39 may also have a small increased risk of having a TP53 mutation.
  • In younger woman with breast cancer, a TP53 mutation may also occur with any of the following features: a family history of cancer, especially LFS-related cancers, a personal history of a breast tumor that is positive for estrogen (ER), progesterone (PR), and HER2/neu markers, also known as “triple-positive” breast cancer, and a personal history of an additional LFS-related cancer.