James N. Ingle, MD, FASCO
Professor of Oncology, Mayo Clinic College of Medicine
Mayo Clinic Cancer Center
Identifying genetic markers that can help select the right endocrine therapy in patients with hormone receptor-positive breast cancer.
Approximately one million patients per year are diagnosed globally with estrogen receptor (ER)–positive breast cancers, which rely on estrogen to grow. This makes them a candidate for endocrine therapy, such as tamoxifen and aromatase inhibitors (AIs), which interfere with hormone signaling. While these therapies are successful in many patients, some do not experience the same benefit and side effects of these treatments can be so harsh that patients suspend therapy. Drs. Ingle, Wang, and their teams are studying how a patient’s genetic makeup can affect tolerance and response to endocrine therapy so that the most effective drugs can be selected. Their findings will ultimately enable doctors to select the best therapy to prevent breast cancer or breast cancer recurrence in women at high risk of the disease.
The team’s studies revealed that differences in the presence and alteration of certain genes can determine how a patient tolerates and responds to endocrine therapies. In addition, they found that the AI anastrozole may affect the body in unanticipated ways. Its main function is to block estrogen production by inhibiting the aromatase enzyme, but the team also found that it binds to the estrogen receptor. Depending on a patient’s estrogen levels, this could have either positive or negative effects, therefore doctors may need to adjust the therapeutic strategy for some patients on anastrozole.
The team previously identified genetic alterations in specific genes that coincide with differences in a patients’ response to AIs—they will study the function of these genes to determine if they directly affect AI response. They will also continue their exploration of anastrozole binding to the estrogen receptor and they will investigate the role of the androgen receptor, another hormone receptor, in ER-positive breast cancers.
James N. Ingle, MD has served in multiple leadership positions within the Mayo Clinic Cancer Center (MCCC); founding Director of the Mayo Clinic Breast Cancer SPORE in 2005; the first chair of the North Central Cancer Treatment Group (NCCTG) in 1978; chair of the NCCTG Breast Committee for 22 years beginning in 1977; chair of the Mayo Clinic Breast Cancer Clinical Trials Committee from for 27 years beginning in 1982; Associate Director for Clinical Research in the MCCC; co-leader of the Women’s Cancer Program in the MCCC; and Associate Director for cancer-related activities for a K30 Clinical Research Training Program Grant. He also served as Director of the SPORE Career Enhancement Program and as Director of the Developmental Research Program.
His primary interests are pharmacogenomics and translational research involving endocrine therapy of breast cancer, and the biology of endocrine sensitivity. His clinical and translational 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.
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