University of Pittsburgh Pittsburgh, Pennsylvania
Professor of Pharmacology and Chemical Biology Professor & Vice Chair for Precision and Translational Pharmacology Director of Education, Women’s Cancer Research Center Magee Women’s Research Institute University of Pittsburgh Cancer Institute
Understanding the biology of invasive lobular carcinoma, a common but understudied form of breast cancer.
Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer after invasive ductal carcinoma (IDC), yet we have a limited understanding of the disease. Despite recent progress, a major challenge is the tremendous heterogeneity within ILC. This has been observed and described by pathologists for many years but has not been studied at the molecular level. Dr. Oesterreich and her team identified a variety of distinct molecular subtypes and variants among ILC tumors that could be very informative for treatment and prognosis. Her hope is that these studies will inform precision medicine for lobular disease.
The team began a detailed analysis of mixed invasive/ductal lobular breast cancer (mDLC), comprehensively characterizing the clinicopathological features of more than 400 mDLC patients. Given that mDLC shares features with both ILC and IDC, it is important to understand how this affects its disease progression, resistance to therapy, and metastasis. They found that while most mDLC’s had features that reflected both IDC and ILC, some features were more closely aligned with ILC. Notably, many cases previously labeled as mDLC in their Cancer Registry were misidentified, pointing towards the potential value of artificial intelligence to increase the precision of diagnoses. The comprehensive review of cases also led to the identification of three new mDLC subclasses.
he team will complete studies that further examine the molecular activities underpinning mixed tumors. In a new project this year, they will explore how the molecule E-cadherin contributes to the differences between ILC and IDC, and if artificially introducing E-cadherin in ILC is sufficient to change it into IDC. This could not only contribute to a fundamental understanding of the disease, but potentially reveal biological drivers that are unique between ILC and IDC—which could be targeted with therapeutic interventions.
The main interest of Dr. Oesterreich’s research is to further our understanding of hormone action in women’s cancer in order to use this knowledge for improved diagnosis and endocrine treatment. Her studies have focused on breast cancer and in receptor action in ovarian cancer. Her lab studies how the estrogen receptor (ER) functions, how its activity is regulated by diverse signaling pathways and through coregulator proteins, and if and how these mechanisms are perturbed in cancer cells. The Oesterreich lab is interested in novel concepts of ER action, such as its role in repression of gene transcription and its role in epigenetic marks in the genome. Dr. Oesterreich’s lab has also a strong interest in situ and invasive lobular disease, with a focus on estrogen and antiestrogen response. In her role as Director of Training in the Women’s Cancer Research Center, she is interested in providing outstanding training opportunities to the next generation of women’s cancer researchers.
2011
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