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Seema Khan, MD
Bluhm Family Professor of Cancer Research
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. She and her team have completed analysis of the first clinical trial to test an anti-progesterone agent in early breast cancer. Insights from these studies 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 determine if a combination of an anti-progesterone drug and anti-inflammatory drug can reduce breast tumor formation.
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 cannot 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 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. Since the progesterone pathway has been shown to be important in the development and progression of breast cancer, it may be targetable with anti-progesterone medications and may provide an alternative approach to prevent breast cancer. Currently, the safety concerns about the use of these medications has precluded their use. Therefore, Dr. Khan and her team are studying new and safer antiprogesterone agents that could improve breast cancer prevention options for high-risk women. Moreover, her team will test these novel agents in combination with an anti-inflammatory agent and determine their utility in preventing breast cancer growth and progression.
Current investigation: She and her team are testing the combination of anti-inflammatory agent (celecoxib) with an anti-progesterone agent (ulipristal) to determine if this combination can reduce the frequency of tumor formation.
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 of BRCA1-deficient breast cancer. They have also shown that there is an increase in the expression of inflammatory proteins in the extracellular matrix of tumors and the levels of one of these, COX-2, can be reversed with an anti-inflammatory agent celecoxib.
What’s next: Dr. Khan and her team will test the novel combination of UPA with celecoxib and determine their effectiveness at reducing tumor formation. The results of their studies will provide a new direction in cancer prevention strategies which will ultimately be translated to clinical trials.
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 Cancer Prevention 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.