Steffi Oesterreich, PhD
Professor of Pharmacology and Chemical Biology
University of Pittsburgh
Director of Education, Women's Cancer Research Center
Magee Women's Research Institute
University of Pittsburgh Cancer Institute
2013-2014 BCRF Project:
Lobular cancers account for 10% to 15% of all breast cancers. Although the incidence of invasive ductal cancers (IDC) has remained relatively constant over the last two decades, there has been a significant increase in the number of invasive lobular cancers (ILC). ILC tumors grow in a long, thin mass, which makes them difficult to detect by mammography. Subsequently, when ILC is diagnosed, tumors are often larger and have more often spread to distant sites compared to IDC. In addition, surgery of ILC is often complicated due to their unique growth pattern, which makes resection and breast conservation approaches more difficult.
Endocrine therapies, or anti-estrogen cancer therapies, are often used to treat ILCs that express the estrogen receptor (also called estrogen receptor positive, ER+). However, a portion of these breast cancers does not respond to these treatments at all. Dr. Oesterreich’s team hypothesized that there are unique features in ILCs that do not respond to endocrine therapies, and that these features are different from the mechanisms underlying endocrine resistance in ER+ invasive ductal cancer (IDC), and which could be clinically targeted.
Dr. Oesterreich has identified unique estrogen responsive genes in tamoxifen resistant lobular cancer cell line models. In 2013-2014, she will now determine if and how these genes may contribute to endocrine resistance, as well as how recruitment of ER (and possible other transcription factors) regulate their expression. Dr. Oesterreich will also expand her studies on the histone deacetylase HDAC7 as one potential candidate for regulating ER’s activity in ILC. Finally, she will increase her efforts in the generation of a well-curated bank of ILC samples to be used for subsequent molecular studies, with the ultimate goal to identify drivers of ILC progression and endocrine resistance.
The focus of Dr. Oesterreich’s project is the analysis unique estrogen and anti-estrogen response in invasive lobular cancer (ILC), which has been chronically understudied, and thus there is limited knowledge about mechanisms of unique action(s) of ER in this disease. The research team has recently finished basic characterization of hormone response in ILC cell lines (Sikora et al, in press, Cancer Research). They are now focusing on the role of specific pathways, including Wnt signaling, in ILC’s estrogen response. In addition, they have completed RNA isolation from a large collection of clinical ILC samples, and are currently preparing to run expression analysis on these samples in order to identify drivers of ILC disease.
The main interest of Dr. Oesterreich's laboratory is to further our understanding of hormone action in breast cancer, with the ultimate goal of using this knowledge for improved diagnosis and endocrine treatment of breast cancer patients. Specifically, Dr. Oesterreich's group studies how the estrogen receptor (ER) functions, how its activity is regulated by co-activator and co-repressor proteins, and if and how these mechanisms are perturbed in cancer cells. Dr. Oesterreich is also interested in novel concepts of ER action, such as its role in repression of gene transcription. Finally, an important goal is the identification of genetic markers such as polymorphisms, or epigenetic changes such as DNA methylation, which might be able to predict a patients response to endocrine therapy, i.e. which can be used to ""personalize medicine."" All of these studies include many aspects of translational breast cancer research utilizing basic biochemistry, molecular and cell biology, cell lines, and clinical samples.