Pathogenic germline PALB2-mutation in a young fеmale patient with breast cancer and its clinical significance: a case report

Abstract

Breast cancer is one of the most common cancer types worldwide and in about 10% of the cases it is associated with a hereditary predisposition. While germline pathogenic variants in the BRCA1 and BRCA2 genes are the likeliest causes for this condition, recently mutations in other genes, with variable penetrance, have been identified. A 34-year-old female diagnosed with triple-negative invasive ductal carcinoma was referred to our genetic counselor. Molecular genetic testing was indicated by the early onset of the disease and the histopathology of the tumor, which however did not identify pathogenic variants in the genes BRCA1 and BRCA2. In search for other contributing genetic factors, we extended the NGS-based diagnostic testing with an expanded Breast Cancer Panel including several more moderate risk genes. Thereby we identified a pathogenic heterozygous germline mutation in the PALB2 gene. This finding may have therapeutic implications for the patient, since currently a potential benefit of PARP inhibitor based therapy is being studied and debated extensively in patients with PALB2-associated cancers. In addition, it has repercussions also for the patient’s carrier-relatives, in the context of a high-risk breast cancer surveillance and prophylactics, some of which are comparable with the recommendations for BRCA-mutation carriers.