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James M. Rae, PhD
Associate Professor of Internal Medicine and Pharmacology
Thomas H. Simpson Collegiate Professorship in Cancer Research
University of Michigan
Ann Arbor, Michigan
Goal: To understand how a patient’s unique genetic makeup can be used to determine whether she will benefit from specific breast cancer therapies.
Impact: Drs. Rae and Hayes have been analyzing tumor tissue and blood samples from thousands of patients with estrogen receptor (ER)-positive breast cancer who are enrolled in a number of large breast cancer clinical trials. They aim to discover genetic predictors of treatment response and toxicities, which will lead to better personalized treatment decisions.
What’s next: The team will continue correlating the genetic makeup of patients with ER-positive breast cancer with response to treatment and side effects.
Most breast cancers require estrogen to grow and can be treated with anti-estrogen therapies such as tamoxifen or aromatase inhibitors. However, not all women with ER-positive breast cancer respond to these medications, and some may experience unwanted side effects. Drs. Rae and Hayes are analyzing patient samples from large clinical trials to understand how inherited genetic factors can affect the tolerance of or response to various types of anti-estrogen drugs.
Full Research Summary
Research area: Identifying inherited genetic markers that will be able to predict whether an individual patient will respond to and tolerate specific anti-estrogen breast cancer therapies.
Impact: Anti-estrogen drugs such as tamoxifen and aromatase inhibitors (AIs) have dramatically improved outcomes in patients with estrogen receptor (ER)-positive breast cancers. But not all women with ER-positive tumors respond to these therapies, and some may experience a cancer recurrence after treatment. Still others may experience toxicities to these therapies. Drs. Rae and Hayes are focused on identifying inherited gene variants that can be used to identify which patients will benefit from endocrine therapy (ET). Their findings could lead to more precise selection of the optimal type of ET and improve treatment adherence to these lifesaving drugs by identifying individual susceptibilities to toxicities.
Current investigation: The team has been genotyping patients enrolled into a number of prospective, randomized clinical trials that have established the role of endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer. The value in using samples from multiple prospective studies includes the large number of patients analyzed, the long-term and detailed clinical follow-up data, the inclusion of control groups, and the ability to validate findings across the different patient cohorts.
What’s next: Drs. Rae and Hayes will continue to correlate patient genotypes with breast cancer treatment response and side effects, which they hope will lead to better personalized treatment decisions.
Dr. Rae received a BS in biology from the University of Pittsburgh and PhD in pharmacology from Georgetown University. In graduate school he combined his interest in breast cancer research with cutting-edge aspects of pharmacology including personalized medicine which uses a patient’s unique genetic makeup to guide treatment decisions. He moved to the University of Michigan in 2001 where he rose to the rank of Associate Professor (with tenure) in the Department of Internal Medicine and holds a joint appointment in the Department of Pharmacology. Dr. Rae’s principal expertise is in the area of cancer drug metabolism, pharmacogenetics/genomics, translational oncology, biomarker identification and characterization, and estrogen receptor signaling, particularly as these may apply to the prediction of breast cancer treatment response. His current research focuses on identifying the subset of estrogen receptor positive breast cancer patients who will respond to endocrine therapy. His work involves two major lines of investigation; one attempts to predict patient response to therapy using a pharmacogenetics approach, while the other seeks to identify and characterize the role of steroid hormone signaling in the growth regulation of breast cancer and the molecular and cellular biology of malignant progression. His work in pharmacogenetics, the study of genetic variability in the way patients respond to medications, involves studies with tamoxifen and aromatase inhibitors and the use of genetic testing to identify patients likely to respond to therapy.