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

Abstract

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 (p=6.05x10-5). 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; p=0.049. Learning disability is associated with CNS tumor and/or optic glioma (OPG); p=0.012. European Americans (EA) are more likely to develop CNS tumor and/or OPG than African Americans (AA); p=0.002. The rate of OPG alone is also higher in EA than AA; p=0.013. Breast cancer is not significantly more prevalent in EA or AA. However, with breast cancer excluded, more EA individuals developed other cancers than AA, p=0.032. 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.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2014
Accession Number
ADA612610

Entities

People

  • Albert M Levin
  • Bruce R. Korf
  • Jaishri O Blakeley
  • Maria Acosta
  • Michael Tainsky
  • Renee Tousignant
  • Xia Wang

Organizations

  • Henry Ford Health

Tags

DTIC Thesaurus Topics

  • African Americans
  • Age Groups
  • Biological Aging
  • Breast Cancer
  • Cancer
  • Carcinoma
  • Cell Physiological Processes
  • Cells
  • Epithelial Cells
  • Genes
  • Genetics
  • Neoplasms
  • Nervous System
  • Neurofibromatosis
  • Neuromuscular Diseases
  • Peripheral Nervous System
  • Skin Diseases

Fields of Study

  • Medicine

Readers

  • Molecular and Cellular Biology
  • Molecular and genetic basis of cancer.