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E. Aubrey Thompson, PhD
Professor of Cancer Biology
Co-director, Breast Cancer Translational Genomics Initiative
Mayo Clinic Comprehensive Cancer Center
- Seeking new therapeutic approaches to ensure long-term, cancer-free survival in breast cancer patients.
Genomic data from large clinical trials are analyzed to identify biomarkers of response and to implement strategies to reduce the risk of recurrence following HER2-directed treatment.
These studies will inform more precise treatment strategies and complimentary therapeutic approaches for patients with HER2-positive breast cancer.
About 15-20 percent of breast tumors are characterized by very high levels of the HER2 protein. About 75-80 percent of HER2-positive breast cancer patients respond well to HER2-targeted therapies like trastuzumab (Herceptin®). The challenge is to figure out how to treat the 20-25 percent of women who do not.
Dr. Thompson and colleagues have shown that the outcome in patients with HER2-positive breast cancer is influenced by several complex factors related to the tumor cells and how they interact with the patient's immune system. A better understanding of the nature of this interaction, how it comes about, how it impacts therapeutic response, and how to manage it is essential to improve patient outcomes.
His group recently reported a striking discovery in patients receiving trastuzumab. Women whose tumors showed an increase in the activation of genes that regulate immune function had a better durable relapse-free survival (the length of time a patient is free of detectable disease) than women whose tumors did not share a similar “immune profile." These findings suggest that the immunological status of the tumor prior to therapy is a key feature in determining the outcome following anti-HER2 therapy.
In continuing studies, Dr. Thompson's group will explore this relationship in more detail using genomic data from large clinical trial cohorts to better understand the risk of recurrence of HER2-positive tumors after treatment with trastuzumab. They will quantify the immune cell composition and activity within breast tumors to make predictions about therapeutic efficacy.
Such information may provide biomarkers that inform the clinician of the probability of a favorable outcome or guide therapeutic decision making (i.e., choice of HER2-targeted therapies).
The ultimate goal is to use this information to develop therapeutic approaches to alter the immune environment in to improve response to therapy and ensure long-term, disease-free survival.
Dr. Thomspon’s core expertise is in cancer genomics. He was a project leader on the FDA-funded MAQCIII project. His was one of three laboratories world-wide to be designated as a primary sequencing lab for this international collaborative study. A member of the breast cancer analytical working group of The Cancer Genome Atlas project, Dr. Thompson heads the breast cancer fusion transcript subgroup. For almost 40 years this work has focused on gene structure and function within the context of the malignant phenotype, with an emphasis on breast cancer. As co-director of the Mayo Clinic Breast Cancer Translational Genomics program, Dr. Thompson coordinates the efforts of a team of highly committed individuals with expertise in computation, biostatistics, bioinformatics, functional genomics, database management, and clinical management of breast cancer patients. This team’s work represents a broad range of collaborations, including basic mechanistic studies, clinical translational studies with a strong focus on analysis of clinical samples and practice-changing discoveries, and development of new tools for genomic analysis. Dr. Thompson’s work is highly translational in nature, and he is motivated by the concept that more effective clinical management of breast cancer requires a more detailed understanding of the biology that underlies the disease. A major objective is to define the genomic architecture of HER2-positive breast cancer, to use this genomic information to identify the biological processes that are associated with clinical outcome, and to use these biological processes to elucidate the biological and genomic basis of therapeutic response.
BCRF Investigator Since
The Play for P.I.N.K. Award