Laura J. Esserman, MD, MBA
Professor of Surgery and Radiology
Director, Carol Franc Buck Breast Care Center
Co-Leader, Breast Oncology Program
UCSF Helen Diller Family Comprehensive Cancer Center
University of California, San Francisco
San Francisco, California
2013-2014 BCRF Project:
(The ANN INC. Award)
Chronic inflammation has been implicated in the initiation and promotion of various cancers, including breast cancer. Tumors are often infiltrated with white blood cells (predominately lymphocytes and macrophages) and the cross-talk between these cells and the cancer cells have profound effects on tumor progression. Dr. Esserman has continued her studies on characterizing and manipulating the tumor immune microenvironment in breast cancer. In the past year, her team completed two preclinical studies demonstrating that a combination of immunomodulating agents targeting tumor associated macrophages (TAMs) and infiltrating T lymphocytes can effectively reprogram the tumor immune microenvironment leading to complete tumor regressions in a model of aggressive triple negative breast cancer.
This past year, Dr. Esserman’s team also initiated collaborations with other researchers to evaluate blood- and tissue-based immune profiling technologies. One blood-based technique, immunosignaturing, is based on the idea that the immune system can be used to assess general health status, and changes in an individual’s immunosignature could indicate the pre-symptomatic presence of various illnesses. Applying this technique to serum samples from women with breast cancer and healthy women, immunosignatures were identified that differentiate breast cancer and healthy serum samples. Dr. Esserman’s team is continuing these immune profiling studies as well as the characterization and manipulation of the tumor immune microenvironment in breast cancer with the goal of bringing new immune-based diagnostic and therapeutic strategies into the clinic.
In a second project, Dr. Esserman will be collaborating with fellow BCRF grantee, Dr. Mina Bissell (Lawrence Berkeley National Laboratory), to focus on ductal carcinoma in situ (DCIS).
Each and every cell in the body is surrounded by a microenvironment, between which there exists a mutual exchange of information that is absolutely required for the development and maintenance of tissues and organs. This exchange, being dynamic, changes continuously depending on the physiological state of the cell, guiding not only development, but also mediating growth, repair, homeostasis, immunity, and all other tissue-specific functions. How the many different types of cells comprising the breast interact with each other and their microenvironment to prevent, or even promote, cancer is still quite mysterious.
In this study, Drs. Bissell and Esserman seek to better understand the earliest malignant changes in cells lining the milk ducts, the architecture of these early DCIS lesions, and the types and functions of cells in these lesions by first gaining a deeper appreciation for the complexity of the normal breast. They plan to fully characterize every cell type within the normal breast, sort them, and maintain them in culture for future studies. Once each of these different cell populations are identified and separated, the investigators will study how they might differ on a gene-transcript level. They will sequence the RNA within each cell population and apply bioinformatic techniques to identify patterns of similarity and difference within each population. Once there is a better understanding of the full catalogue of cells and their gene transcript signatures in the normal breast, Drs. Bissell and Esserman will use a similar approach in studying the relative cellular makeup of DCIS. Through this approach, they expect to gain a fuller understanding of the role of the different cellular components in normal physiology and how they give rise to DCIS.
Dr. Esserman’s current studies are aimed at improving the systemic anti-tumor immune response generated by local treatment. In addition to developing immunotherapeutic strategies to remodel the tumor immune microenvironment, her team is also interested in better characterizing the immune landscape in the context of breast cancer, both systemically (in the blood) and locally (in the tumor tissue). Previously they found that immunosignatures based on the specificities of antibodies that are present in an individual’s blood could differentiate between serum samples from women with breast cancer and serum samples from healthy volunteers. They have continued these studies with an improved immunosignaturing platform and will be expanding their analyses to women with DCIS as well as women from Nigeria (both patients with breast cancer and healthy Nigerian women). The researchers are continuing these immune profiling studies as well as the characterization and manipulation of the tumor immune microenvironment in breast cancer with the goal of bringing new immune-based diagnostic and therapeutic strategies into the clinic.
A second project, conducted jointly with Dr. Mina Bissell at Lawrence Berkeley National Laboratory, is focused on DCIS. The context in which each cell and tissue finds itself is a key determinant of breast cancer development and progression. In order to understand the events that lead to the development of DCIS (ductal carcinoma in situ), abnormal premalignant lesions within the breast ducts that could very well be precursors to malignant tumors, researchers must first characterize the microenvironmental contribution of every cell type within the normal breast- and the DCIS. Previously Dr. Bissell’s team at Lawrence Berkeley National Laboratory (LBNL) initiated development of methods to identify the distinct cell types of the normal breast by immunostaining, to separate the fractions using a Fluorescence Activated Cell Sorter (FACS), and discovered that the human mammary gland contains at least a dozen different types of cells, and they are proceeding to develop protocols to maintain each of these sub-populations in culture. Similarly methods to study the role of macrophages and other cells of the immune system have been developed in the Esserman Laboratory. In the first three months of the current BCRF award to Drs. Esserman and Bissell, the two groups have exchanged protocols and expertise. Some of the protocols developed by LBNL group for normal breast will be adapted for the on-site study of DCIS tissues from the UCSF operating theatres. In addition, RNA sequencing has become a powerful method to characterize how any given cell type is functioning, and to characterize its distinct biological activities using cells from reduction mammoplasty. The researchers have just isolated sufficient numbers of cells by FACS from each sub-population to isolate RNA from each, so that they can sequence the RNA and apply ‘bioinformatic’ techniques to identify patterns of similarity and difference of gene expression within each population. They expect to gain a fuller understanding of the role of the different cellular components in normal breast physiology, leading to understanding which populations are involved in the etiology of DCIS.
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.
In addition, Dr. Esserman is the Principal Investigator of the I-SPY TRIAL program, a multi-site neoadjuvant clinical trial that has evolved into a model for translational research and innovation in clinical trial design. Dr. Esserman has recently launched a University of California-wide breast cancer initiative called the Athena Breast Health Network, a project designed to follow 400,000 women from screening through treatment and outcomes, incorporating the latest in molecular testing and web-based tools into the course of care.