ABSTRACT
PURPOSE: We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients. METHODS: This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes. RESULTS: 144 patients were tested (113 somatic, 21 germline, and 10 both). Technical issues prevented the analysis of 23 prostatic samples (18.7%). 12 (8.3%) patients had HRD. BRCA2 was the most frequent mutation (66.7%). Patients with HRD were younger (57.5 years). Patients with BRCA mutations had poorer survival (31.9 vs 56.3 months, p = 0.048). CONCLUSION: In our institution, 8.3% of the patients had HRD. Tumor tissue analysis failed in 18.7% of tests. ctDNA analysis is an alternative detection method. BRCA mutations are correlated with poor prognosis.
Subject(s)
BRCA2 Protein , Homologous Recombination , Prostatic Neoplasms , Humans , Male , Retrospective Studies , Middle Aged , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/mortality , Aged , BRCA2 Protein/genetics , Mutation , Prognosis , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Aged, 80 and over , Germ-Line Mutation , BRCA1 Protein/genetics , AdultABSTRACT
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.
Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , Bone Neoplasms , Li-Fraumeni Syndrome , Humans , Li-Fraumeni Syndrome/genetics , Tumor Suppressor Protein p53/genetics , Adrenocortical Carcinoma/genetics , Germ-Line Mutation , Adrenal Cortex Neoplasms/genetics , Genetic Predisposition to DiseaseABSTRACT
Advanced breast cancer represents a challenge for patients and for physicians due its dynamic genomic changes yielding to a resistance to treatments. The main goal is to improve quality of live and survival of the patients through the most appropriate subsequent therapies based on the knowledge of the natural history of the disease. In these guidelines, we summarize current evidence and available therapies for the medical management of advanced breast cancer.
Subject(s)
Breast Neoplasms , Physicians , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/therapy , GenomicsABSTRACT
Colorectal cancer is the first cause of cancer in occidental countries if we consider both male and females tumours. In Spain, 26,000 new cases are diagnosed every year. The possibilities of cure are higher if the tumour is diagnosed early. One of the most important risk factors for colorectal cancer is inheritance. Some hereditary syndromes, such as familial adenomatous polyposis (FAP), increase the risk by almost 100% and at a young age. Other more prevalent syndromes, such Lynch syndrome, increase the risk 10-12 times more than in the general population. This article aims at summarising the most important aspects in hereditary colorectal cancer and to be a useful tool to oncologists who work with these patients and their families.