Seema Khan, MD
Bluhm Family Professor of Cancer Research
Professor of Surgery
Feinberg School of Medicine
Investigating the role of the progesterone pathway in breast cancer causation, prevention, and treatment.
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 prophylactic mastectomy is not a preferred option for healthy 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 chemoprevention for breast cancer. Currently, safety concerns of anti-progesterones have precluded their use in this setting. Therefore, Dr. Khan and her team are studying new and safer anti-progesterone agents that could improve breast cancer prevention options for high-risk women. They will apply their findings to a new cancer prevention strategy, combining the blockade of both progesterone action and inflammation.
In preclinical studies, Dr. Khan 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. Moreover, the preventive effect was related to the suppression of hormone signaling as well as the suppression of inflammation. Laboratory studies have been conducted to determine if a combination of UPA and an anti-inflammatory drug can reduce breast tumor formation. Preliminary analysis reveals the combination as a promising alternative to single therapies.
Dr. Khan will continue to analyze the results of her preclinical studies and conduct studies to determine the lowest level of UPA that will be effective in reducing breast tumor formation. Her team will also continue their ongoing work to test the novel combinations of UPA and an anti-inflammatory agent, combining the blockade of both progesterone action and inflammation. In addition, Dr. Khan is exploring drug delivery vehicles to more effectively target agents into breast tissue. In the next year, she will synthesize nano-carriers of UPA and test their efficacy in delivering this agent to mammary tissue. If successful, these pre-clinical studies will support the feasibility of using these drug-loaded carriers to directly administer UPA and endoxifen trans dermally and ultimately help translate their use into the clinic with the potential to prevent tumor formation.
Seema A. Khan, MD 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.
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