Kim Hirshfield, MD, PhD

2009-2010 BCRF Project:
The Regina Quick Award
Co-Investigator: Arnold J. Levine, PhD, The Institute for Advanced Study, Princeton, and the Cancer Institute of New Jersey, New Brunswick

Genetic variations between individuals can confer a risk for the development of breast cancer, the age of onset of a breast cancer, the response to treatment and the risk of recurrence. Genetic variations in a set of genes, termed the p53 pathway genes, deal with our ability to respond to stress such as chromosome damage, nutritional depravation, heat or cold shock and the exposure to chemical mutagens and carcinogens. The goal of this research is to identify women at higher risk for developing breast cancers at young ages so they may begin more intensive screening to detect such cancers at an early stage. In addition, the researchers are uncovering risk factors for relapse after cancer treatment so that these women may be either treated differently or followed more closely. They have surveyed 142 genes in the p53 pathway for evidence of alleles that are under positive or negative selection over recent evolutionary time frames. Of those, they have identified eight single nucleotide polymorphisms in eight genes that appear to have a functional activity that is under selection pressure. Of these, five SNPs impact upon an early developmental stage in human embryos and two SNPs have demonstrated reproducible evidence of increasing the incidence and lowering the age of onset of breast cancers in humans.

Mid-Year Progress Report:
Drs. Hirshfield and Levine have identified polymorphisms in two genes that regulate the levels and activity of a tumor suppressor gene, p53, in preventing breast cancers from arising in women. These polymorphisms lower the age of onset and increase the frequency of different kinds of breast cancers. They have been able to reproduce this observation in a laboratory model that develops breast cancers which now permits the researchers to explore environmental variables, estrogen levels and other factors that might impact upon tumor development. In addition they have uncovered a potential polymorphism in parents that may transmit higher error rates, polymorphisms or copy number variations of genes (CNVs), to their children. They are testing the possibility that one of these CNVs plays a role in the inherited basis of breast cancers.

Bio:
Kim M. Hirshfield obtained her B.S. from Rutgers University and her Ph.D. in Biology with distinction in Biochemistry from Johns Hopkins University. She received her M.D. and completed residency in Internal Medicine and fellowship in Medical Oncology at UMDNJ/Robert Wood Johnson Medical School. Her medical training was followed by a post-doctoral fellowship with Dr. Arnold J. Levine at The Cancer Institute of New Jersey. Dr. Hirshfield is now an Assistant Professor in the Department of Medicine, Division of Medical Oncology at UMDNJ/Robert Wood Johnson Medical School where she specializes in early stage breast cancer and pre-malignant breast abnormalities at The Cancer Institute of New Jersey.

Dr. Hirshfield has an ongoing clinical trial to explore genetic determinants of breast cancer while also building a clinical database and sample repository at The Cancer Institute of New Jersey. Her specific research interest focuses on single nucleotide polymorphisms in genes of the p53 pathway and their contribution to clinical parameters such as risk, age of onset of breast cancer, and recurrence. Several polymorphisms are under study, especially as they play a role in hormone responsive breast cancers. Further laboratory work is aimed at elucidating the molecular mechanism behind these clinical findings.