The Risk and Clinical/Molecular Characteristics of Breast Cancer in Women with Neurofibromatosis Type 1

The purpose of the project is to characterize the breast cancer in women affected with Neurofibromatosis type 1 NF1 in a multi-institutional setting. Aim 1 assessed the incidence of breast cancer in this cohort and the clinical features of NF1 associated with breast cancer and other cancers. Aim 2 investigated the NF1 gene germline mutations in women with breast cancer. A total of 423 cases of NF1 women have been reviewed. History of breast cancer was found in 20. Family history of cancer is associated with a personal history of breast cancer p6.05x10-5. No other clinical feature or family history is found to be significantly associated with the occurrence of breast cancer. Malignant peripheral nerve sheath tumor MPNST is associated with plexiform neurofibromas p0.049. Learning disability is associated with CNS tumor andor optic glioma OPG p0.012. European Americans EA are more likely to develop CNS tumor andor OPG than African Americans AA p0.002. The rate of OPG alone is also higher in EA than AA p0.013. Breast cancer is not significantly more prevalent in EA or AA. However, with breast cancer excluded, more EA individuals developed other cancers than AA, p0.032. To date, germline NF1 mutations has been investigated in 14 women with breast cancer history. Four 28 are mutations affecting in-frame splicing, possibly more than average NF1 cases. Aim 3 has not been completed yet. Aim 4. NF1 inactivation results in human mammary epithelial cells HMEC senescence p53 inactivation does not rescue the senescence phenotype in NF1KD knockdown HMEC p53 inactivation provides an initial growth advantage to HMEC with a consequent large number of cell death Overexpression of K-Ras V12 does not transform p53 inactivated HMEC.