Mayo Clinic Cancer Center
Professor of Oncology, Mayo Clinic College of Medicine
Identifying genetic markers that can help select the right endocrine therapy in patients with hormone receptor-positive breast cancer.
Every year, approximately one million women globally are diagnosed 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 individuals at high risk of the disease.
The team previously identified genetic alterations in specific genes that coincide with differences in a patients’ response to AIs. They subsequently found that these alterations modify the production of other genes, and they are exploring how those genes function within tumors and under the effect of AIs. In addition, they explored how breast cancer might become resistant to the AI anastrozole. They found that anastrozole treatment prevents the destruction of a protein called fatty acid synthase (FASN), which leads to increased breast cancer cell growth. High levels of FASN are associated with poor outcomes in anastrozole-treated patients, and FASN could serve as a new therapeutic target in endocrine-resistant breast cancer.
In addition to continuing their exploration of how genetics impacts patient response to AIs, the team is exploring the role of the androgen receptor (AR), another hormone receptor, in ER-positive breast cancers. They have found an interesting relationship between the ratio of androgen of two hormone receptors, AR and ER, that may dictate how a tumor responds to AR or ER-blocking therapies. In addition, they are exploring new ways that the AR-targeting therapy, enzalutamide, may function in ER-positive tumors, and they are exploring that further.
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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