RESUMO
Li-Fraumeni syndrome is caused by heterozygous germline pathogenic variants in the TP53 gene. It involves a high risk of a variety of malignant tumors in childhood and adulthood, the main ones being premenopausal breast cancer, soft tissue sarcomas and osteosarcomas, central nervous system tumors, and adrenocortical carcinomas. The variability of the associated clinical manifestations, which do not always fit the classic criteria of Li-Fraumeni syndrome, has led the concept of SLF to extend to a more overarching cancer predisposition syndrome, termed hereditable TP53-related cancer syndrome (hTP53rc). However, prospective studies are needed to assess genotype-phenotype characteristics, as well as to evaluate and validate risk-adjusted recommendations. This guideline aims to establish the basis for interpreting pathogenic variants in the TP53 gene and provide recommendations for effective screening and prevention of associated cancers in carrier individuals.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Neoplasias Ósseas , Síndrome de Li-Fraumeni , Humanos , Síndrome de Li-Fraumeni/genética , Proteína Supressora de Tumor p53/genética , Carcinoma Adrenocortical/genética , Mutação em Linhagem Germinativa , Neoplasias do Córtex Suprarrenal/genética , Predisposição Genética para DoençaRESUMO
OBJECTIVE: Randomised clinical trials with a control arm of non-screened patients are nowadays ethically impossible. The aim of this study was to establish the impact of mammography screening on a non-selected population. PATIENTS AND METHODS: Between January 1993 and December 2002, 3662 patients were included, 2313 in the screened group and 1349 in the unscreened group. RESULTS: 55.3% of the screened patients were diagnosed in stage I vs. 26.1% in the non-screened group. The proportion of stage III-IV was 4.6% and 19.8% for the screened and unscreened groups respectively (p<0.001). 48.8% in the screening group were submitted to mastectomy vs. 66.4% of the unscreened patients (p<0.001). Overall survival was superior for the prevalent cases in the screening group, with a relative risk of 0.49, and was not significant for the incident cases. CONCLUSIONS: Diagnosis of breast cancer in the mammography screening programme of the Region of Valencia significantly increases conservative surgery rates and suggests an improvement in survival in prevalent cases. The increased rate of early stages in these patients could be the main reason of this benefit.