关键词：乳腺癌；临床医学；基因
摘 要：The purpose of this project is to characterize the breast cancer in women affected with Neurofibromatosis type 1 (NF1) in a multi-institutional setting. The first aim is to assess the incidence of breast cancer in this cohort and the clinical features of NF1 associated with breast cancer. The second aim is to investigate any characteristic NF1 gene germline mutations in women with breast cancer and to carry out whole exome sequencing to search for other germline mutations. For the third aim, at tumor tissue level, we plan to characterize the selected signaling pathway on archived breast cancer tissue from women with NF1 utilizing immunohistochemistry (IHC) methods. At the somatic level, we plan to study loss of heterozygosity (LOH) of the NF1 gene using ion semiconductor sequencing and MLPA copy number analysis. We also plan to sequence 30 other breast cancer genes on the breast cancer specimens. By the end of May, 2013, a total of 242 cases of NF1 women have been reviewed. Eleven women have had a diagnosis of breast cancer. Statistical analysis was conducted. The presence of plexiform neurofibroma has a trend to be inversely related to the occurrence of breast cancer, however, it has not reached statistical significance (p=0.083). A family history of cancer is associated with a personal history of breast cancer (p=0.000119). No other clinical features or family histories were found to be associated with the occurrence of breast cancer. To date, germline NF1 mutations has been investigated in 10 women with breast cancer. No significant pattern of mutation has been discovered. Nine breast cancer specimens have been collected and are ready to be analyzed. We are expected to review up to 450 cases of women with NF1 and collect another 5 archived breast cancer specimens. The analyses listed in the above aims are to be completed once the final cases have been reviewed and the specimens have been collected.