Germline mutations in NF1 and BRCA1 in a family with neurofibromatosis type 1 and early-onset breast cancer

Abstract

Neurofibromatosis type 1 (NF1) is a common dominant autosomal disorder caused by mutations in the NF1 gene. The main manifestations of NF1 are café-au-lait spots, neurofibromas, intertriginous freckling, Lisch nodules, and malignancy, including peripheral nerve sheath tumors, central nervous system gliomas, and a variety of other tumors not so clearly defined. The association between NF1 and breast cancer or other gynecologic malignancies seems uncommon and has been scarcely referred in the literature. We describe a family with two females affected by both NF1 and early-onset breast cancer, and a male with NF1. We evaluated whether the concomitance of both disorders could be attributed to a NF1 mutation and its supposed increased risk of breast cancer or to the concurrence of two NF1 and BRCA1/2 germline mutations. Mutation analyses identified a frameshift mutation in BRCA1 and a nonsense mutation in NF1. Our findings stress the importance of considering all phenotypic features in families with both NF1 and breast tumors. To offer a specific risk assessment and management of both conditions, NF1 and BRCA1/2 cancer predisposing genes should be analyzed.

Oral Metastasis of Metaplastic Breast Carcinoma in a Patient with Neurofibromatosis 1

“…Furthermore, most cases were ductal invasive carcinoma and less commonly lobular carcinoma (Table 2) [5–7, 11–31]. Interestingly, we found one well-documented case of MBC (carcinosarcoma) [11].…”

Metaplastic spindle cell carcinoma of the breast in a patient with neurofibromatosis type 1

“…Neurofibromin, the protein encoded by the NF1 gene, functions as a negative regulator of the ras oncogene pathway. Ras is an essential component of the signal transduction pathway that regulates cell growth, proliferation, differentiation, and apoptosis, and the impairment of the hydrolytic reaction is associated with an increased risk of cancer . Yoon et al have reviewed all of the reports of breast cancer in NF1 patients.…”

Infiltrating Ductal Carcinoma of Breast with Coexistent Neurofibroma-A Rare Association

“…The mastectomy specimen showed a foci of neurofibroma with benign clusters of peripheral nerves admixed with fibroblasts, which showed diffuse positivity for S100. To the best of our knowledge, Campos et al were the only group to report a family with individuals with diagnosis of NF1 and breast cancer who were carriers of both BRCA1 and NF1 mutations [12]. They concluded that the concurrence of NF1 and breast cancer was probably due to the simultaneous existence of two cancerpredisposing conditions.…”

“…They concluded that the concurrence of NF1 and breast cancer was probably due to the simultaneous existence of two cancerpredisposing conditions. Most of the cases of breast cancer in NF1 individuals are diagnosed at an advanced stage with a T score greater than 2 [12,13]. Therefore, the worse prognosis of breast cancer in NF1 may not be a characteristic of the disease itself, but may result from late-stage diagnosis due to the presence of skin neurofibromas, which hinder its identification, or due to the delay in seeking medical care by patients who think the breast mass is a neurofibroma [14,15].…”