W. Fraser Symmans, MD
Professor and Director of Research Operations, Department of Pathology
Professor of Translational Molecular Pathology
Developing gene-based prognostics tests to guide treatment decisions for patients with estrogen receptor-positive breast cancer.
Most breast cancers are driven by hormones, particularly estrogen. These cancers, referred to as estrogen receptor (ER)-positive, are treatable with anti-hormone (endocrine) therapies. As breast cancers progress, however, they often lose sensitivity to endocrine therapy. This is particularly true in breast cancers that have spread to other tissues—a process called metastasis. Dr. Symmans is developing a series of gene-based tests referred to as SET (Sensitivity to Endocrine Therapy) that can be used to guide treatment decisions in patients with metastatic (stage IV) or regional (stage II-III) breast cancer. This assay employs advanced technology and has the potential to allow more precise treatment decisions compared to current assays—this is vital for the clinical management and improvement of outcomes for breast cancer patients with aggressive and advanced breast cancers.
Dr. Symmans has demonstrated that the SET2,3 test (used to predict sensitivity to endocrine therapy for Stage II or III breast cancer) is technically accurate and reliable. Moreover, the SET2,3 test adds significant additional information to current prognostic tests such as OncotypeDX® or MammaPrint®. This is most likely due to the improved measurement of endocrine sensitivity. Building on their success with SET2,3 with endocrine therapy, Dr. Symmans expanded his focus to examine its accuracy in predicting and quantitating benefit from chemotherapy. His team showed that 86 percent of patients with high SET2,3 measures were disease-free at five years versus 69 percent of patients with low SET2,3 measures. The prognostic value of SET2,3 remained significant at 10 years with nearly 78 percent of SET2,3 high patients being disease-free versus 58 percent of SET2,3 low patients. Low SET2,3 levels, however, were found to be predictive of response to dose-dense chemotherapy—identifying patients most likely to benefit from this therapy and sparing those less likely to benefit. Other studies demonstrated that the SET4 test that combines measurements of gene expression signatures and gene mutation for Stage IV breast cancer is highly reproducible.
Based on promising predictive results for patients with stage II, III and IV ER-positive breast cancer, Dr. Symmans' team will continue to determine how SET2,3 and 4 should be used to guide therapy planning. In addition, Dr. Symmans and his colleagues will determine if the duration of chemotherapy affects the sensitivity to subsequent endocrine therapy as measured by the SET assay.
Dr. Fraser Symmans is Professor and Director of Research Operations in the Department of Pathology at MD Anderson Cancer Center, where he practices Breast Surgical Pathology and Cytopathology and also directs the Breast Cancer Pharmacogenomics Laboratory. He received his medical degree from the University of Auckland, New Zealand, completed his residency at Columbia University, New York, and fellowship at MD Anderson Cancer Center, Houston. Dr. Symmans joined the faculty of New York University Medical Center in 1993 and moved to MD Anderson Cancer Center in 2000. Dr. Symmans’ research is focused on breast cancer, with specific emphasis on neoadjuvant (pre-operative) treatment trials for evaluation of chemosensitivity and development of diagnostic tests to select the most effective treatments for individuals with breast cancer. This research program has led to the development of predictive molecular tests that are currently being evaluated in a prospective clinical trial. His other ongoing research is addressing the effects of biopsy sample quality on genomic test results in order to establish appropriate best practices for clinical diagnostic use. Additional responsibilities include: Co-Chair for the Translational Breast Cancer Research Consortium, Director of Translational Research Program for the Alliance clinical trials group, and member of the Breast Cancer Steering Committee for the National Clinical Trials Group.
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