Seema Khan, MD

2012-2013 BCRF Project:
(made possible by generous support from ANN INC.)

Progesterone is an important culprit in breast cancer causation, and new anti-progesterone drugs (CDB 4124 and its derivatives) offer an important but so far unutilized opportunity for breast cancer prevention. One of the barriers to the use of these drugs in healthy women who are at high risk of developing breast cancer is the presence of side effects on the liver, irregular menstrual bleeding, and others. The chemical structure of these anti-progesterone drugs makes them suitable for delivery through the skin of the breast (local transdermal therapy, or LTT); previous studies of tamoxifen and related agents suggest that LTT will avoid side effects by providing effective concentrations in the breast, but very low concentrations in the rest of the body. Dr. Khan’s team will continue to screen a number of anti-progesterone drugs to identify the agents with the best ability to get through the skin (permeation), test methods for further improvement of permeation, and identify the most permeable drug that is also the most effective against a laboratory model of breast cancer. Future plans include the testing of the most suitable anti-progesterone agent in models that include spontaneous and progesterone-pathway-specific tumor models, and then in early-phase clinical trials.

Mid-year Progress: The overall goal of Dr. Khan's team is to develop anti-progesterone drugs for breast cancer prevention and therapy. They have selected the drug CDB4124 (Proellex) as the candidate most suitable for development at this time and are testing its mechanisms of action against breast cells in the laboratory, along with development of a clinical trial to test it for the first time as a breast cancer agent in humans. Their work in the laboratory has shown that CDB4124 retards the binding of the progesterone receptor to the genes that are regulated by progesterone, and by synthetic progesterone-like drugs. In this way, it inhibits the effects of progesterone on breast cells.

On the clinical trial front, Dr. Khan's team is making good progress and hope to have their first trial open by March 1, 2013. The protocol has been approved by the Lurie Cancer Center Scientific Review Committee, it is under review by the Northwestern University Review Board, and the team has responded to initial comments from the Food and Drug Association and hope to have approval within the next few weeks. This trial will test for the first time whether a short course of therapy with CDB4124 during the "window" of time between diagnosis and surgery will decrease the growth rate of breast cancer cells and change the gene expression in the cells in a favorable direction. The successful completion of this trial will set the stage for studies where the drug is given for several months, to healthy high risk women, and to those with newly diagnosed breast cancer.

Bio:
Dr. Khan joined the Northwestern faculty in 2000 to develop a program in basic science research for breast cancer. She is Co-Leader of the Lynn Sage Comprehensive Breast Center and Director of the Bluhm Family Program for Breast Cancer Early Detection and Prevention.

As a leader in new breast cancer research in assessing the association between nipple fluid hormones, gene methylation levels and risk of breast malignancy, Dr. Khan also conducts clinical trials of cancer chemoprevention agents. She is Northwestern's principal investigator for the breast cancer trials of the National Surgical Adjuvant Breast and Bowel Project and the American College of Surgeons Oncology Group. She chairs a National Cancer Institute Division of Cancer Prevention protocol investigating the effects of a soy supplement on the breast epithelium of women at high risk of breast cancer. She is also co-investigator on a study of the role of alpha-B crystallin expression in breast cancer biology and was principal investigator on a recent study of ductal lavage biomarkers in high-risk women.

Dr. Khan is an associate member of the Early Detection Research Network and has served on the National Consortium of Breast Centers board of directors and the endocrinology review panel of the Department of Defense. She has also served on peer-review panels of the National Cancer Institute, the Avon Foundation, and the Susan G. Komen Foundation. She is a founding member of the board of directors of the International Society of Cancer Risk Assessment and Management and is a member of the breast cancer screening panel of the National Comprehensive Cancer Center Network. She belongs to many professional societies, including the American College of Surgeons and the Society for the Study of Breast Disease.

Dr. Khan has published more than 70 peer-reviewed articles as well as six book chapters and 90 abstracts. She is on the program committee of the American Society of Clinical Oncology and will serve as track leader for breast cancer for its 2009 annual meeting. She is a member of the editorial board of the Journal of Clinical Oncology and serves as a reviewer for many professional journals.