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Seema Khan, MD
Bluhm Family Research Professor of Breast Cancer
Professor of Surgery
Feinberg School of Medicine
Goal: To identify alternative approaches for breast cancer prevention in high-risk women.
Impact: Dr. Khan is investigating the role of the progesterone pathway in breast cancer causation and prevention—and possibly in treatment as well. She and her team have completed analysis of the first clinical trial to test an anti-progesterone agent in early breast cancer. Dr. Khan’s insights could lead to new advances in prevention and therapy for women at a high risk of breast cancer.
What’s next: Dr. Khan will conduct laboratory studies to identify changes in the mammary glands that relate to successful prevention of breast cancer and will apply that data to the design of clinical trials to test a combination therapy that includes an anti-progesterone drug.
Women who have a high risk of breast cancer or breast cancer recurrence may require anti-estrogen therapy or surgical removal of their breasts to reduce their chance of getting cancer. While these approaches are effective, there are few options for women who can’t tolerate anti-estrogen therapy or who want to keep their breasts. Dr. Khan is exploring the potential value of anti-progesterone strategies, which appear to be a promising prevention and treatment strategy for this group of women.
Full Research Summary
Research area: Investigating the role of the progesterone pathway in breast cancer causation and prevention, and also potentially in treatment.
Impact: Effective preventive measures, including anti-estrogen therapy and surgical removal of the breasts, are available for women who are at high risk of breast cancer or breast cancer recurrence. However, not all women can tolerate anti-estrogen therapy, and others want to keep their breasts.
The progesterone pathway is important in the development and progression of breast cancer, so anti-progesterone medications could be an alternative approach. However, these have not been used because of safety concerns and unproven effectiveness. Using laboratory models, Dr. Khan is studying new (and safer) anti-progesterone agents that could improve prevention options for high-risk women.
Current investigation: She and her team are exploring the changes that occur in the mammary gland stem cell compartment as a result of progesterone receptor inhibition and have also been working on a wide-ranging analysis of the first clinical trial to test an anti-progesterone agent in early breast cancer.
What she’s learned so far: Dr. Khan has found that the anti-progesterone drug telapristone decreases tumor formation in a laboratory model, and that the related drug ulipristal acetate (UPA) does the same in a model with a defective BRCA1 gene.
What’s next: The team will test the combination of UPA with an active metabolite of tamoxifen, called endoxifen. They also plan to study gene and protein expression in mammary glands before the development of tumors to identify pathways that are associated with successful prevention of breast cancer.
Dr. Seema A. Khan is Professor of Surgery in the Feinberg School of Medicine at Northwestern University, and the Bluhm Family Professor of Cancer Research. She is the Co-leader of the Women’s Cancer Research Program at the Robert H. Lurie Comprehensive Cancer Center. Her research focuses on applying biomarker knowledge to improve breast cancer risk stratification and develop preventive interventions for high risk women. Her research is funded by the NIH (NCI), The Breast Cancer Research Foundation, the Avon Foundation, and the Susan G. Komen Foundation.
Current studies include an examination of the effects of progesterone antagonists in women with breast cancer, and a study of breast cancer risk biomarkers in benign breast biopsy samples. In addition, Dr. Khan’s group is working on the development of transdermal delivery of drugs to the breast. She chairs a Phase III trial for the Eastern Cooperative Oncology Group which will investigate the role of local therapy for the primary tumor in women presenting with Stage IV breast cancer. Recently completed research includes a case/control study of hormone levels in nipple aspirate fluid.