Laura J. Esserman, MD, MBA

2007-2008 BCRF Project:
Dr. Esserman and her colleagues are conducting an investigation of inflammatory cells or macrophage involvement in aggressive breast cancers; a clinical biomarker trial using the anti-inflammatory agent, statins, and a national trial of imaging and molecular markers to rapidly assess response to chemotherapy in locally advanced cancer. In the macrophage study, they are looking for the presence of "rogue" or proliferating macrophages in breast cancer in two sets of banked breast tumor tissues from UCSF and West Africa. They are working to find the best and most reliable markers of these cells, which they hope will serve as intermediate markers for targeted drug trials.

In the coming year, they plan to develop studies to test three new therapeutic approaches to eliminating the rogue macrophages. They will simultaneously test these in laboratory models, and develop clinical protocols for early testing in the clinic using the short term drug exposure model. Their ultimate goal is to find the optimal way to introduce new treatments to alter the disease course and improve survival in patients whose tumors are driven by "inflammatory" pathways.

In the second project, they are studying the impact of short exposure of the cholesterol lowering and anti-inflammatory "statin" drug on breast cancers in the period of time between diagnosis and surgical treatment. They have nearly completed enrollment for this multi-center trial. They expect to complete their ongoing clinical trial in a month or so, complete the tissue biomarker studies, analyze the trial results and plan to present the results for presentation/publication.

Finally, in the I SPY trial, women with tumors of at least 3 cm in size who are treated with chemo-therapy prior to surgery undergo both Magnetic Resonance Imagining (MRI) and tissue sampling at four time points during therapy. With BCRF funding, the researchers were able to review all of the pathology and to test a model of residual disease at the time of surgery as a predictor of recurrence. They were able to train 8 pathologists across the country to participate in this study, using online web training and online tools to support data capture and analysis.

In the coming year, the researchers will analyze the results of laboratory tests to measure the protein levels in tumors. These tests can shed light on the various pathways in a tumor cell and will hopefully give clues as to which pathways are turned on and off when a person’s tumor responds to chemotherapy. If the researchers better understand which pathways to target when a tumor does not shrink when chemotherapy is given, they should be able to more intelligently design new therapies and work more efficiently to test treatments that have the greatest hope of working.

Mid-Year Progress Report:
This year, Dr. Esserman and her team are conducting an investigation of inflammatory cells or macrophage involvement in aggressive cancers, and a clinical biomarker trial using the anti-inflammatory agent, statin. For the first project, the researchers are looking for the presence of "rogue" or proliferating macrophages in breast cancer using two sets of banked breast tumor tissues from UCSF and West Africa. They are working to find the most robust and reliable marker that can identify these cells and serve as intermediate markers for targeted drug therapies. They have continued to analyze cases with long-term follow-up to assess the importance of macrophages in breast cancer, specifically focusing on proliferating macrophages or promacs. These promacs are characterized by the expression of specific cell surface proteins. The researchers are in the process of evaluating markers of these cell surface proteins to reliably identify the presence of promacs. Three markers of interest that they are currently evaluating are MAC387, Tie2, and CSF1-R.

The second BCRF project looks at statins, drugs that are used to reduce cholesterol, and are emerging as agents capable of affecting inflammatory pathways – potentially critical cancer pathways. This trial explores the short-term impact of an established health-promoting drug, fluvastatin, on DCIS and early breast cancer lesions. The trial, "Randomized Phase II Biomarker Pilot Trial of Fluvastatin Use in Women with Ductal Carcinoma in Situ (DCIS) or Stage I Breast Cancer", has accrued 8 patients to the randomization arm and 2 patients to the control arm since July 2007 and has been closed to accrual. This trial is exploring the impact of a 3 to 6 week course of 20 or 80 mg of Fluvastatin on the cancer cells of women with DCIS or stage 1 cancer. The researchers are currently in the process of conducting immuno-histochemical staining of all breast cancer tissue specimens that were collected. An initial database has been built and data cleaning and entry are in process. Preliminary results for this trial will be reported within the next 3-4 months.

Finally, Dr. Esserman reports that the I-SPY amended protocol is now open for accrual at 6 of the 9 study institutions. Ten patients have been enrolled in the past two months, and accrual should increase rapidly as the remaining sites open.

Bio:
Laura Esserman is Professor of Surgery and Radiology at the University of California, San Francisco (UCSF) and the Director of the UCSF/Mt. Zion Carol Franc Buck Breast Care Center. Dr. Esserman received her undergraduate degree from Harvard and her MD from Stanford University, where she completed her surgical residency and an oncology fellowship. After completing her medical training, she was awarded a Hartford Fellowship to enable her to pursue her MBA at the Stanford University School of Business. Dr. Esserman has a joint appointment in the Departments of Surgery and Radiology and is affiliate faculty for the Institute for Health Policy Studies and Medical Informatics Program. She is also the Co-leader of the Breast Oncology Program of the UCSF Cancer Center.

Dr. Esserman's practice is devoted to diseases of the breast, particularly breast cancer. At the Breast Cancer Center, patients are looked at as a whole person, and are not identified by their disease. This philosophy is behind Dr. Esserman's interest in helping women become more involved in their own decision making process. The Center is designed to advance the state of the art of delivering breast healthcare through better tools for risk assessment, better prediction of benefit from intervention, knowledge integration across the many disciplines and providers involved in care delivery, and integration of clinical research into the patient care process. The Center was created as part of a multi-million dollar grant, one of three awarded nationally, from the Department of Defense. Novel approaches include the introduction of a collaborative care decision focused model, where patients and physicians make decisions together, and the introduction and testing of tools to use risk assessment and new biological markers explicitly in therapeutic decision making.

Dr. Esserman is also involved in research and furthering the knowledge of providers as well as patients. Current projects include: the development of a vaccine for treatment of ductal carcinoma in situ; clinical trials designed around biomarkers; and developing MRI imaging as a surrogate marker of disease and response in order to improve cancer staging and enable the introduction of novel therapeutics. She also speaks extensively at many public and private forums and has published numerous articles covering a broad range of topics, from immunology to health policy and health care delivery. The philosophy underlying Dr. Esserman's research and practice is to ensure that a patient’s sense of comfort, knowledge, and participation are central in delivering the best care possible.