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