James N. Ingle, MD
Head, Breast Cancer Research Program, Mayo Clinic Cancer Center
Foust Professor of Oncology, Mayo Medical School, Rochester, MN
2009-2010 BCRF Project:
(made possible by generous support from Play For P.I.N.K.)
Tamoxifen remains one of the most important drugs for the treatment of breast cancer and recent information indicates that a patient's genetic make-up is related to tamoxifen's metabolism (called pharmacogenetics) and the amount of benefit a patient receives. The Mayo Clinic researchers have discovered that the different metabolites of tamoxifen have different effects on the estrogen receptor, explaining the impact of CYP2D6 genotype on clinical outcomes seen in women treated with tamoxifen. This knowledge provides the basis for developing true personalized endocrine therapy of breast cancer.
The studies proposed for the coming year will provide important information regarding ERβ, its impact on, and relationship to, ERα, in terms of tamoxifen metabolite action. In addition to providing knowledge about endocrine biology, the research will determine if ERβ can be used as a predictive factor and/or target for selective endocrine therapy in women with breast cancer, which would lead to more personalized therapy.
Mid-Year Progress Report:
Tamoxifen remains one of the most important drugs worldwide for the treatment of breast cancer. Dr. Ingle and colleagues have previously demonstrated, with BCRF support, that endoxifen is the most potent tamoxifen metabolite in cells expressing estrogen receptor (ER) á, the type of ER measured in a patient's breast cancer. These studies support the findings in patients which demonstrate that women with genetically impaired metabolism of tamoxifen have significantly reduced endoxifen levels and a higher risk of breast cancer recurrence. Data has emerged suggesting that the presence of the other type of ER, ERâ, in breast cancers may be related to increased benefits from tamoxifen therapy. The researchers have discovered that endoxifen's actions on ERâ differs from that on ERá. The current work is directed at understanding the role of ERâ in sensitivity to hormonal therapy, in general, and to endoxifen, in particular. This research has the potential to markedly improve hormonal therapy for women with breast cancer.
Bio:
Dr. Ingle is Professor of Oncology and Foust Professor in Mayo Clinic College of Medicine. He is the leader of breast cancer research in the Mayo Clinic Comprehensive Cancer Center serving as Program Co-Leader of the Women's Cancer Program with responsibility for breast cancer. Dr. Ingle is the Director of the Mayo Clinic Breast Cancer Specialized Program of Research Excellence. He was chair of the Breast Committee of the North Central Cancer Treatment Group for 22 years (1977-1999).
His primary interests are pharmacogenomics and translational research involving endocrine therapy of breast cancer and the biology of endocrine sensitivity. He has 270 peer-reviewed publications. He has served on numerous national and international bodies such as the NIH (1990) and St. Gallen (2003-2009) Consensus Conference Panels on early breast cancer, serving as Co-Chair of the 2009 St. Gallen Conference. He currently serves on the Breast Cancer Steering Committee of the NCI Coordinating Center for Clinical Trials.
