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James N. Ingle, MD
Co-Director, Mayo Clinic Breast Cancer SPORE
Mayo Clinic Cancer Center
Foust Professor of Oncology
Mayo Clinic Medical School
- Seeking to identify biomarkers that can predict who is most likely to benefit from anti-estrogen prevention therapy.
- Studies are ongoing to explore potential genetic markers related to effectiveness of tamoxifen and aromatase inhibitors.
- This work may lead to a more personalized approach to prevention that is based on a woman's genetic makeup.
The majority of breast cancers rely on the hormone estrogen for growth. Anti-estrogen therapies are effective at both treating and preventing this kind of breast cancer- called estrogen receptor (ER)-positive. Side effects from hormonal therapy, however, cause many women to stop taking it. Drs. Ingle and Wang are conducting studies to understand how a woman’s genetic makeup affects her response to anti-hormone therapy. They hope to identify genetic markers that can help select the best preventive therapy for each woman.
Full Research Summary
Tamoxifen and raloxifene belong to a class of anti-estrogen drugs called SERMs and are effective agents for the chemoprevention of breast cancer. However, many women at high risk for breast cancer will not take these drugs due to the potential for toxicity. Women differ in their genetic make-up, and this variability can determine how a woman tolerates and responds to drugs such as tamoxifen and aromatase inhibitors.
The focus of Drs. Ingle and Wang's research is to identify biomarkers that can predict who is most likely to benefit from SERM prevention therapy and aromatase inhibitors. They have identified two genetic markers that appear to be associated with response to SERM treatment. The same genes are involved in regulation of the BRCA genes, and so they may also be important in selecting patients for PARP inhibitor therapy, a therapy that has been approved to treat advanced BRCA-related breast and ovarian cancers.
These findings indicate that, for the first time, breast cancer prevention therapy may be able to be "personalized" by using genetic biomarkers. The team will continue to explore the genetic differences related to effectiveness of tamoxifen and aromatase inhibitors.
Their ultimate goal is to establish the genetic basis for selecting the best endocrine therapy treatment for a given woman, either to prevent breast cancer when she is at high risk or to prevent recurrence when she has already been diagnosed.
James N. Ingle, MD 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 Co-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. His clinical research has impacted clinical practice. He has served on numerous national and international bodies such as the NIH (1990, Conference Vice-Chair) and St. Gallen (2003-2013) Consensus Conference Panels on early breast cancer (Co-Chair of the 2009 St. Gallen Conference), and the NCI Breast Cancer Steering Committee.