Not just a ‘usual’ Li-Fraumeni syndrome

BJMO - volume 14, issue 3, may 2020

Y. Dockx MD, A. Goossens MD, J. Decloedt MD, R. de Putter MD, M. Vandewalle MD, W. Lybaert MD


The Li-Fraumeni syndrome (LFS) is characterised clinically by the appearance of tumours in multiple organs, generally at an early age. This hereditary condition is caused by germinal mutations in the TP53 gene, which codifies for the tumour suppressor gene p53.

We present here the case of a patient aged 40 with the diagnosis of LFS who presented with premenopausal breast cancer. She had a positive family history of cancer. As a consequence, she was referred to genetic counselling. Genetic analysis revealed a TP53 germline mutation, which is diagnostic for LFS. However, further genetic analysis of different tissues showed a genetic mosaicism in our patient.

Patients with LFS have a high risk for a broad spectrum of tumours. The diagnosis and management of Li-Fraumeni syndrome should be performed by a multidisciplinary team, and genetic counselling should be offered to patients and their relatives. Targeted next-generation sequencing represents an efficient approach for the identification of mutations in families with a heterogeneous phenotype. Theoretically, since mosaics do not have mutations in all of their cells, the cells that do not have mutant p53 are less likely to undergo malignant transformation or have the same risk of everyone else.

(BELG J MED ONCOL 2020;14(3):100–105)

Read more

Diagnosis of Li-Fraumeni syndrome just in time to prevent iatrogenic secondary cancer

BJMO - 2019, issue 2, february 2019

Y. Dockx MD

A 40-year old patient presented with a lump in the left breast which prompted her to seek medical attention. There was a positive family history for different cancers. MRI mammae showed two lesions highly suspicious of cancer, one identified as an invasive ductal adenocarcinoma (IDA), the second as a ductal carcinoma in situ (DCIS). Biopsy of a visible axillary lymph node was positive for IDA. ER and PR were highly positive, with HER2-negativity. Tumor marker CA15.3 was normal. CT-scan thorax/abdomen and bone scintigraphy showed no evidence of distant metastases.

She underwent left radical mastectomy + axillary lymph node dissection. Microscopic evaluation of the surgical specimen revealed a moderately differentiated IDA (T=1.6cm) and DCIS (T=8.5cm) and one out of nine positive lymph nodes (pT1cpN1acM0).

Adjuvant chemotherapy (4 cycles dose dense epirubicin-cyclophosphamide followed by 12x weekly paclitaxel), radiotherapy on left chest wall/lymph nodes and hormonal treatment were scheduled.

After the last paclitaxel, genetic testing revealed Li-Fraumeni syndrome (LFS), just before initiation of irradiation. LFS is characterized clinically by the appearance of tumors in multiple organs generally at an early age. This autosomal dominantly inherited condition is caused by germline mutations of the tumor suppressor gene TP53. Lifetime breast cancer risk is 49% by age 60. Because of a higher radiosensitivity in LFS with 40% risk of radiation-induced second cancer (mostly soft tissue sarcoma), radiotherapy was abruptly cancelled. She was subsequently started on combination endocrine therapy triptorelin + letrozole for 5 years.

She is currently undergoing intensive cancer surveillance (e.g. full body MRI, endoscopy) as per recently revised guidelines (= modified Toronto protocol), because riskof cancer development isstrikingly high in LFS. If a strict adherence can be maintained, the overall survival outlook is promising. The demonstration of a TP53 mutation in our patient means that her first-degree relatives also have a 50% risk of being carrier of the mutation. They are eligible for presymptomatic screening from newborn age.

Patient will undergo a risk reducing contralateral mastectomy with reconstruction in the near future. Also handling with the psychosocial aspects of individuals and families with LFS is a challenge for a multidisciplinary team.

Read more