Kim M. Hirshfield
Robert Wood Johnson Medical School
Dept. of Medicine - Medical Oncology
The Cancer Institute of New Jersey
195 Little Albany Street
New Brunswick, NJ 08903-2681
Breast cancer, high risk breast abnormalities, translational research, genetic contributors to breast cancer risk and outcomes
The majority of patients diagnosed with breast cancer have no known risk factors including identifiable genetic alterations such as BRCA1 and BRCA2. Abnormalities in components playing a critical role in cell growth and regulation or coordination of cell checkpoint functions in both hereditary and sporadic breast cancers including p53. Regulation of p53 can be altered by upstream or downstream elements. We have previously described the role of the single nucleotide polymorphism SNP309 in the mdm2 gene, the main negative regulator of p53, in the development of earlier age of onset of breast cancer. The identification of single nucleotide polymorphisms (SNPs) that may confer increased susceptibility and prognostic significance in breast cancer patients has significant implications for identification and treatment of individuals at risk. We are actively studying other SNPs including those in Akt1, mdm4, p53, p53BP1, perp, PP2A, GRM1, MNTR1A/B, and E-cadherin for their role in breast cancer risk and outcome measures. We are exploring other pathways and presence of copy number variants for their contributions to breast cancer phenotypes. We have an ongoing IRB-approved protocol (CINJ# 040406) that has accrued 2,000 individuals. Of these nearly 80% have been diagnosed with breast cancer and the remaining controls to evaluate genetic risk factors for development of breast cancer. DNA from breast cancer patients and healthy controls is being analyzed for the presence of polymorphic variants and statistical analyses performed to determine presence of clinical associations. The purpose of our studies are to determine (1) the relationship between polymorphisms in genes involved in tumor biology and (a) risk of and age of onset of breast cancer (b) risk of and time to recurrence; and (2) to define the molecular mechanisms of SNPs with a clinical phenotype using in vitro model systems.