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Risk Management for Li-Fraumeni Syndrome (p53) Mutation Carrier
Li-Fraumeni Syndrome (LFS) is due to a germline mutation in the p53 gene. It is an autosomal dominant condition.
This risk management guideline has been developed for individuals who have NOT been diagnosed with a relevant cancer.
It also excludes
- Individuals < 18y
| Cancer | p53 mutation carrier | General population up to the age of 85 yrs |
|---|---|---|
| Cancer (female) | 50% by 30 yrs 80% by 40 yrs >90% by 50 yrs |
33% |
| Cancer (male) | 20% by 30 yrs 30% by 40 yrs 60% by 50 yrs |
50% |
| Breast (female) | high but not quantified other than increased relative risk |
11% |
| Sarcoma | high but not quantified other than increased relative risk |
not available |
| Brain – various | high but not quantified other than increased relative risk |
0.8% |
| Adrenocortical carcinoma | high but not quantified other than increased relative risk |
not available |
| Others: leukaemia, malignant phyllodes tumour, Wilm’s tumour, peripheral nervous tumours, lung, colon and pancreatic cancer |
Colon cancer, earlier onset (mean age 33y) and overall lifetime RR 2.8 Other tumours, raised risk and/or earlier onset but not quantified |
not available |
The published literature is biased towards families meeting classic diagnostic criteria or with high cancer incidence.
Cancer Management Guidelines
There is currently no international consensus on screening. Management should occur in conjunction with local specialists, ideally in a single service with expertise in LFS.
General
Annual clinical review with clinical examination by a designated specialist.
Encourage early reporting of symptoms.
Clinicians need to be aware of the increased risk for rare malignancies and the increased risk of a second malignancy.
Breast
Surveillance
Breast awareness from the age of breast development.
Recommended Screening
- starting at 20 years
- Annual MRI’s between 20 and 50 years
- Other imaging (mammography +/- USS) should only be considered if unable to access MRI
If pregnant or lactating – consider USS
Risk Reducing Medications
No reported study specifically in p53 mutation carriers
Lifetime risk is sufficient to consider offering
Surgery
Bilateral risk reducing mastectomy at 40 or younger confers the greatest reduction in risk.
Breast self-awareness should continue post-surgery.
Sarcoma, Brain, Haematological Cancers, Adrenocortical Tumours and other cancers
Surveillance
Limited evidence for a benefit of screening of other cancer types. Should be considered through multidisciplinary services with expertise in LFS and include awareness of and prompt reporting of any new symptoms, annual full clinical examination with further investigations as clinically indicated.
Colorectal Cancer
Consider colonoscopy every 2-5 years from 25 years (or younger if there is a family history of colon cancer)
Gastric Cancer
Consider gastroscopy every 2-5 years from 25 years (or younger if there is a family history of gastric cancer)
Prevention
- Avoid unnecessary radiation exposure for screening or therapeutic purposes
- Avoid smoking and excessive sun exposure
- Avoid the use of combination HRT beyond 50 years
The impact of lifestyle on cancer risk should be discussed (e.g. encourage exercise, maintenance of a healthy weight, limiting alcohol intake, breast feeding)
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