A Paternally Inherited BRCA1 Mutation Associated with an Unusual Aggressive Clinical Phenotype

This report highlights the necessity of genetic testing, at least for BRCA1 mutations, of young females diagnosed with triple negative breast cancer, even in the absence of or limited family history. A 34-year-old female with a locally advanced, triple negative tumour, which perforated the skin, is described. At the time of diagnosis, the patient had already multiple lung metastases and although chemotherapy was started immediately, she died with rapid systemic disease progression. The patient was found to carry the BRCA1 p.E1060X mutation, which is located on exon 11 of the gene. The high penetrance of BRCA1 gene is not represented in the patient’s family, since the mutation was paternally inherited. It is evident that females belonging to small families, along with paternal inheritance of pathogenic BRCA mutations that predispose for breast cancer, in most cases will probably be genetically tested only after being diagnosed with cancer. 1. Introduction BRCA1 and BRCA2 genetic testing has been available in the clinic at least for the past decade, allowing the characterization of people that face an increased breast and ovarian cancer risk. Although the selection criteria for genetic testing are quite established, many times the small size of the family or the paternal inheritance of the pathogenic BRCA mutation can be misleading when referring patients. Therefore, loss-of-function mutations can be genetically transmitted from male BRCA mutation carriers, who can be in many cases cancer-free, to their daughters, who will have a lifetime breast cancer risk that can be as high as 84% [1–3]. Estimated lifetime breast cancer risk for male BRCA2 carriers is approximately 8% [4], while there is high relative risk for pancreatic and prostate cancer, when compared to the general population [5]. On the contrary, relative and cumulative cancer risks are much lower in male BRCA1 carriers [6]. Since our current knowledge is advanced on understanding the cancer predisposition of mutation carriers, it seems rather important to successfully identify these individuals in order to offer appropriate clinical management. 2. Case Report A 34-year-old premenopausal female with a locally advanced tumour presented as a dirty ulcer, perforating the skin, in her right breast is described. Biopsies of the damaged tissue showed an invasive, grade III ductal carcinoma, with areas of papillary shaping, areas of necrosis, and invasion of the skin. The breast tumour was classified as triple negative, since there was a lack of estrogen and progesterone receptor expression and absence