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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.
The patient's immune system has a lot to do with how she or he responds to treatment. Dr. Thompson is conducting studies to understand how the tumor cells interact with the immune cells, to learn how to use this information to predict therapeutic response, and to discover ways to boost the patient's immune system to more effectively kill tumor cells.
Full Research Summary
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 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.
This year, the team is investigating how anti-tumor immune response is influenced by where the immune cells are located within the tumor and its surrounding areas. This information will inform additional studies to test hypotheses about the relationship between immune function and treatment outcome. The long-term goals are to identify women who may be at risk of recurrence or, optimally, may require less aggressive therapy and to develop therapeutic approaches 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