Kim Hirshfield, MD, PhD

2008-2009 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.

Drs. Hirshfield and Levine have identified genetic variations in four genes in this pathway that increase or decrease these cancer risks and are exploring how these variations act to initiate a cancer, respond to environmental changes or respond to treatments for breast cancers. 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.

Mid-year Progress Report:
Cancers arise because of mutations in a specific set of genes producing proteins that fail to function properly, resulting in too much cell division or too little cell death. These mutations can occur spontaneously in a tissue (somatic mutations) or can be inherited (such as BRCA-1). We also inherit a large number of differences in our genes that contribute to our individuality and diversity among people. These many small differences are called polymorphisms and the simplest type of polymorphism is termed a single nucleotide polymorphism or SNP.

Drs. Levine and Hirschfield and their colleagues have been able to identify SNPs in three genes that contribute to the origins and age of onset of breast cancers and other cancers. They have identified a gene whose SNP is regulated by estrogen and so it functions only in younger, premenopausal women with estrogen receptor positive breast cancers. A second SNP acts only in ER-negative breast cancers. Two of the genes involved (MDM-2 and MDM-4) regulate the third gene, p53. These same genes and SNPs play a role in regulating fertility in women by their involvement in the production of LIF, a cytokine required for implantation of embryos into the uterus.

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.