Li-Fraumeni Syndrome (LFS) is an inherited familial predisposition to a wide range of certain, often rare, cancers. This is due to a change (mutation) in a tumor suppressor gene known as TP53. The resulting p53 protein produced by the gene is damaged (or otherwise rendered malfunctioning), and is unable to help prevent malignant tumors from developing. Children and young adults are susceptible to developing several multiple cancers, most notably soft-tissue and bone sarcomas, breast cancer, brain tumors, adrenocortical carcinoma and acute leukemia. Other cancers seen in LFS patients include gastrointestinal cancers and cancers of the lung, kidney, thyroid, and skin, as well as in gonadal organs (ovarian, testicular, and prostate.)

It is important to note that not everyone with a TP53 gene mutation will necessarily develop cancer, but the risks are substantially higher than in the general population. A diagnosis of LFS is critically important so that affected families can seek appropriate genetic counseling as well as screening for early detection of cancer. lfsassociation.org

At this time, there is no standard treatment or cure for LFS or a germline TP53 gene mutation. With some exceptions, cancers in people with LFS are treated the same as for cancers in other patients, but research continues on how to best manage those cancers involved in LFS.

Children (birth to age 18 years)

General assessment
- Complete physical exam every 3-4 months
- Prompt assessment with primary care physician for any medical concerns

Adrenocortical carcinoma
- Ultrasound of abdomen and pelvis every 3-4 months
- In case of unsatisfactory ultrasound, blood tests every 3-4 months

Brain tumor
- Annual brain MRI (first MRI with contrast – thereafter without contrast if previous MRI normal with and no new abnormality)

Soft tissue and bone sarcoma

Annual whole body MRI

Adults

General assessment
- Complete physical exam every 6 months
- Prompt assessment with primary care physician for any medical concerns

Breast cancer
- Breast awareness (age 18 years and forward)
- Clinical breast exam twice a year (age 20 years and forward)
- Annual breast MRI screening (ages 20-75) – ideally, alternating with annual whole body MRI (one scan every 6 months)
- Consider risk-reducing bilateral mastectomy
  - (Note that the use of ultrasound and mammography has been omitted)

Brain tumor (age 18 years and forward)
- Annual brain MRI (first MRI with contrast – thereafter without contrast if previous MRI normal)

Soft tissue and bone sarcoma (age 18 years and forward)
- Annual whole body MRI
- Ultrasound of abdomen and pelvis every 12 months

Gastrointestinal cancer (age 25 years and forward)
- Upper endoscopy and colonoscopy every 2-5 years)

Melanoma (age 18 years and forward)
- Annual dermatologic examination

Also noted, for families in which breast cancer has already made an appearance at or around age 20 – awareness and screening can be considered 5 to 10 years before the earliest age of onset known. The same is recommended for gastrointestinal cancers – consider screening 5 years before the earliest known onset of a gastrointestinal cancer in the family.

See Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome (June 2017) for more information.