Katherine L. Nathanson, MD

2009-2010 BCRF Project:
Many families with multiple cases of breast cancer do not have detectable mutations in BRCA1 and BRCA2, and the genetic risk responsible for cancer in these families is unclear. Variation in gene copy number may explain the excess cancer seen in some families. In this study, Dr. Nathanson and her colleagues focus on identifying additional genes or genetic variants that underlie breast cancer susceptibility in high risk families. To address this question, they are evaluating, in families with multiple cases of early onset breast cancer, whether they can identify if any change in the copy number of genes, sequence of genes known to be associated with BRCA1 or novel genes are associated with disease.

Mid-Year Progress Report:
Dr. Nathanson and colleagues are in the process of examining copy number variation and single nucleotide polymorphisms that co-segregate with breast cancer in high risk BRCA1/2 negative families. They have participated in multiple studies as part of an international consortium to identify genetic variation that modifies risk to BRCA1/2 mutation carriers. They are interested in examining cancer risk in families for which the reason for cancer is unknown, and for individuals who test negative for a known BRCA1 or BRCA2 mutation in the family. In the last year, the researchers have examined the risk of breast cancer in women who test negative for known familial BRCA1/2 mutation. Although several small studies have shown an elevated risk in these individuals, the researchers’ larger study did not identify any elevated risk of breast cancer for those women, a crucial piece of information in clinical management.

Bio:
Dr. Katherine Nathanson received her BS in Biology with Honors from Haverford College and her MD from the University of Pennsylvania School of Medicine. She then trained in Internal Medicine at the Beth Israel Hospital, Boston and did a fellowship in Genetics at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania. She is doubly boarded in Internal Medicine and Genetics. She completed her postdoctoral laboratory training with Dr. Barbara Weber in the University of Pennsylvania School of Medicine, focusing on breast cancer genetics.

Dr. Nathanson has had a long-standing interest in the genetics of breast cancer and her studies in breast cancer have focused on three areas. During her fellowship, she has led several studies that focused on characterizing BRCA1 and BRCA2 mutations in different patient populations for which she received the AFLAC Scholar-In-Training award. She also has participated in studies identifying genetic modifiers of penetrance in BRCA1 and BRCA2 mutation carriers, examining both candidate modifiers of penetrance with Dr. Timothy Rebbeck and using linkage based methods to identify novel modifiers of penetrance. She has participated in the Breast Cancer Linkage Consortium effort to identify novel genetic variants that increase susceptibility to breast cancer, such as CHEK2. Dr. Nathanson's current efforts continue these studies and have expanded to include characterization of breast cancer on a genomic level to identify both somatic and germline genetic changes important in breast cancer.