Titles and Affiliations
Bluhm Family Professor of Cancer Research
Professor of Breast Surgery
Feinberg School of Medicine
Research area
Investigating the role of the progesterone pathway in breast cancer causation, prevention, and potential 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, safety concerns about these medications have precluded their use. 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.
Progress Thus Far
The overarching goal of Dr. Khan’s work is to develop two complementary prevention strategies: a novel combination of two re-purposed drugs and a unique drug delivery system. Her BCRF-funded work has shown that combining two repurposed FDA-approved drugs–ulipristal acetate (a progesterone-blocking pill used for fibroids and as a post-coital contraceptive) and celecoxib (an anti-inflammatory medication)—prevented breast tumor formation in 75 percent of BRCA1-deficient laboratory models, while each drug alone had weak effects. They also showed that a skin-applied Z-endoxifen gel (Z-ENX-TE) can penetrate through breast skin models and reduce cell growth.
What’s next
Dr. Khan will continue build on her pre-clinical findings and determine if the combination of ulipristal acetate and celecoxib can also prevent the more common hormone-sensitive breast cancers. If the combination is effective, this would provide a rationale for its testing across all high-risk women regardless of genetic mutation status. In parallel, her team will use advanced drug-imaging methods to assess whether Z-ENX-TE can travel throughout the breast. Additionally, they will determine if its biological effects in the breast can be detected by MRI. Their results will help guide the design of the next phase of testing in women at high-risk for breast cancer. Together, these studies aim to provide safe, effective, and broadly applicable breast cancer prevention options for all high-risk women.
Read more about Dr. Khan’s work as part of BCRF’s Precision Prevention Initiative here.
Biography
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.
