Kim Hirshfield, MD, PhD

2007-2008 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

Cancers arise because of mutations in a specific subset 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 or be inherited (such as BRCA-1) and those combinations result in earlier age of onset and higher probabilities of developing breast cancers. In addition to mutations, as individuals we inherit many differences in our genes that contribute to the diversity among people. These differences are called polymorphisms. When they occur as simple changes in our chromosomes (DNA) they are called single nucleotide polymorphisms, or SNPs.

Drs. Hirshfield and Levine have been able to identify SNPs in a set of genes that raise the frequency and lower the age of onset of a specific subtype of breast cancer (estrogen receptor and progesterone receptor positive) in pre-menopausal women. They have begun to understand how estrogen regulates the expression level of this gene and why that results in less protection from breast cancer mutations. These observations help to explain the value and functions of anti-estrogen therapy for these tumors. This may also explain why some post- menopausal women are at a higher risk of developing breast cancers when they take estrogen supplements.

The researchers continue to look for additional polymorphisms, or SNPs that have an impact upon the origins, treatment responses, and outcomes of breast cancers. They have preliminary evidence for a novel SNP that may predispose some breast cancer patients to a higher rate of primary or secondary site relapses of their cancers. This SNP is in a gene that plays a role in adhesion between breast cells. If correct and confirmed, this observation could permit the identification of women at higher risk for cancer relapses.

Mid-Year Progress Report:
Drs. Hirshfield and Levine have been able to identify SNPs in several 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, pre-menopausal women with estrogen receptor positive breast cancers. They have recently devised a new method to identify genes and SNPs that play both a role in the origins of cancers and the responses to treatment of cancers, and are presently testing the roles of these SNPsin breast cancer patients.

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.