Li-Fraumeni syndrome (LFS), also known as the sarcomacancer arising from bones and/or soft tissue, breast, leukaemiacancer of blood and/or blood forming tissues and adrenal gland (SBLA) cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndrome, is a rare genetic disorder that causes the development of multiple malignantcancerous, may grow and spread to other areas of the body tumours throughout the body at a very young age. It is caused by a genetic mutation in the p53 gene, also known as the TP53 gene, which acts as a tumoura tissue mass that forms from groups of unhealthy cells suppressor in the body.
Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
LFS is slightly more common in females, and tends to develop before the age of 40 (often in childhood before the age of 10). However, anyone can develop this disease.
Types of Tumours Associated with Li-Fraumeni Syndrome
LFS is most commonly associated with the development of various sarcomas, breast cancers, leukaemia’s, and adrenal gland cancers. However, it has also been linked to other types of tumours, such as brain tumours. Some examples include:
- Sarcomas (most common), such as:
- Breast cancer.
- Leukaemia’s, such as:
- Adrenal gland cancers, most notably adrenocortical carcinoma.
- Brain tumours, such as:
Rarely, other types of tumours may develop as a result of LFS, such as:
- Mouth cancer
- Lung cancer
- Prostate cancer
- Melanoma (cutaneous)
- Wilms’ tumour
- Stomach cancer
- Colorectal cancer
- Pancreatic cancer
- Oesophageal cancer.
- Germ cell tumours.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cellsthe basic structural and functional unit of all living things look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, each patient with LFS will present with a unique disease behaviour, with varying cancer locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of cancer present
- Cancer location
- Whether or not the cancer has metastasised
- Your age
- General health
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for tumours associated with LFS may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible – these will vary based on tumour type and location.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Immunotherapya treatment that uses a person's immune system to fight cancer.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Cryotherapythe process of freezing off cancerous tumours and/or lesions using liquid nitrogen.
- Hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone (for certain receptor positive breast cancers).
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells (common with leukaemia).
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Li-Fraumeni Syndrome and Radiation Therapy
Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, or radiotherapy, uses controlled doses of radiation to damage or kill cancer cells. This is one of the more commonly known cancer treatments, however, there is evidence to suggest that patients with LFS are more sensitive to radiation, and have a higher risk of developing radiation-induced tumours. Patients with this condition may be advised to be cautious about the use of radiotherapy as a treatment option.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of LFS has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them. For patients with LFS, the screening guidelines differ between children and adults.
Childhood LFS Screening Guidelines
For children with LFS, screening guidelines may include:
- Complete physical exam every 3-4 months.
- Abdominal and pelvic ultrasounds every 3-4 months.
- Blood teststesting done to measure the levels of certain substances in the blood every 3-4 months.
- Annual MRI of the brain and whole body.
Adult LFS Screening
For adults with LFS, screening guidelines may include:
- Complete physical exam every 6 months.
- Clinical breast exam every 6 months.
- Annual MRI of the breasts, brain, and whole body.
- Annual abdominal and pelvic ultrasounda type of medical imaging that uses sound waves to create detailed images of the organs and structures within the pelvis, including the uterus, ovaries, and surrounding tissues.
- Upper endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs and colonoscopyan examination of the large intestine/bowel with a small, flexible instrument known as a colonoscope every 2-5 years.
- Annual skin checks.
Screening options for LFS may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
While the cause of LFS remains unknown, the following factors may increase the likelihood of developing the disease:
- Certain genetic mutations, such as TP53 and CHEK2 (another tumour suppressor gene).
- Having a family history of Li-Fraumeni syndrome.
Individuals with LFS may also be prone to carcinogenic risks (a substance that has the potential to cause cancer), such as tobacco smoking or radiation exposure.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
The symptoms of LFS often vary by the type(s) of tumours present. General symptoms of LFS may include:
- Swelling and/or lump(s) in affected regions.
- Neurological changes, potentially including:
- Seizures.
- Headaches
- Nauseato feel sick or likely to vomit and/or vomiting.
- Changes in walking.
- Fevers.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Easy bruising and/or bleeding.
- Bone pain.
Symptoms related to specific tumours can be found on our knowledgebase.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have LFS, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
If your doctor suspects you have LFS, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Genetic testing.
- Neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination.
- Endocrine studiesstudies that involve blood, urine and/or imaging tests to analyse hormone levels.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body
- Lumbar puncturea procedure that involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebrospinal fluid (CSF) for analysis.
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow..
- Exploratory surgeryan exploratory surgical procedure used for conditions that cannot be confirmed by scans and tests alone.
- Biopsyremoval of a section of tissue to analyse for cancer cells.