Etiology and Prevention: Finding the Underlying Causes
Overview: Although our foundation of knowledge for the basic science aspects of breast cancer (tumor biology) has expanded greatly over the past decade, there still remains a gap in our strategies for large-scale prevention due to uncertainties over the underlying causes of the disease and their relative importance. There is an extensive list of factors associated with increased or decreased risk for breast cancer. However, some of these factors (such as diet) remain controversial; how others affect breast cancer (such as socioeconomic status) remains a mystery, and true causes are yet to be discovered.
Etiology/Prevention topics are particularly difficult to address. In 2009 we are attacking the question through eight primarily large-scale funding efforts including our Special Research Initiatives and Core Funding’s translational research award.
Etiology & Prevention Portfolio
If a woman was exposed to chemicals years ago, could that cause breast cancer today? Barbara Cohn at the Public Health Institute is undertaking a five year, $5 million study to find out if women exposed to certain chemicals while they were developing in the womb are more likely to get breast cancer. Exposure to endocrine disrupting chemicals (EDCs) in the fetus is thought to increase breast cancer risk, yet the decades-long gap to actual breast cancer incidence makes this connection difficult to prove. With rare access to samples taken from pregnant women 40 years ago, Dr. Cohn and her team will look at levels of toxins and breast cancer in the daughters. The propspective nested case control study will measure the differences between an estimated 112 cases and 336 controls in CHDS daughters. This project will also look to see if exposures to those EDCs differ between women by race/ethnicity, neighborhood, and education.
Peggy Reynolds and Susan Hurley of the Northern California Cancer Center will investigate how we can use California’s unique resources to identify breast cancer risk factors across the State. They are undertaking a one-year pilot project to develop methodology that will allow them to augment the California Teachers Study with more diverse members, collect more biological samples, and develop the most feasible and useful study for this unique cohort and data resource. The resulting research questions and study design will be reviewed in 2010 for up to $6 million, multi-year research into the environment's role in breast cancer. This project is supported in part from a grant from the Avon Foundation for Women.
With so many risk factors acting together to cause breast cancer, how can we understand and prevent it? Robert Hiatt of the University of California, San Francisco will lead a two-year project to develop a model for conceptualizing breast cancer causation and prevention approaches that includes combinations of interacting causes, such as genes, breast tissue structure, hormones, chemicals from the environment, events during development in the womb, diet, immigration history, barriers to exercise due to neighborhood, income and education level, social support, and cultural attitudes about breastfeeding. The result will be an evidence-based tool to improve research design and policy decisions.
To take advantage of new, more powerful computers and software, the CBCRP is funding research teams to develop new statistical analysis strategies and apply them to existing data sets. David Nelson of the Northern California Cancer Center will examine which, if any, of the thousands of pesticides used in California agriculture pose a risk of breast cancer to our state’s teachers. The resulting modeling tool will be made available to other environmental health and breast cancer researchers. Eric Roberts with the Public Health Institute will use advanced computer power to make breast cancer data more useful for researchers, the public, and advocates. His lab will create tools for exploring smaller geographic differences in breast cancer in California, while protecting patient privacy and allowing for the addition of other area-specific characteristics to identify vulnerable communities and generate new research ideas.
Identifying chemicals that increase the risk of breast cancer can lead to risk reduction through public health measures to reduce exposure. To understand which chemicals pose a risk, the CBCRP funded a conference award to Lawrence Kushi from the Kaiser Foundation Research Institute. A scientific workshop on November 17, 2009, brought together biologists and regulatory toxicologists. The goal is to develop standard methods for describing changes in mammary gland structure and development, and to recommend chemical tests that regulatory agencies can use to more thoroughly assess their effect on mammary glands. The conference will be held in conjunction with the annual meeting of the National Institutes of Environmental Health Sciences Breast Cancer and Environment Research Centers (BCERC).
As we gain a greater understanding of the risk factors for developing breast cancer, that information must be used to devlop strategies to reduce the risk. A soy isoflavone compound, called genistein, preferentially binds to one type of estrogen receptor (ER-beta) more than to another type of estrogen receptor (ER-alpha) and may inhibit the growth-stimulating effects of activation of the estrogen receptor alpha. Soy isoflavones may act as possible Selective Estrogen Receptor Modulating agents. Epidemiological studies in Asian populations have found that consuming more high soy-containing foods is associated with lower breast cancer risk. Anna Wu from the University of Southern California will conduct a three-year study to determine whether soy isoflavones supplements can be used to protect women at high risk of developing invasive breast cancer. Dr. Wu’s team will conduct a double-blinded randomized study of 100 women of varying ages and ethnicities with DCIS and of women at high risk of developing breast cancer based on BRCA mutation and Gail model scores. Mammographic breast density, MRI breast volume, blood samples, and a breast biopsy will be obtained before and after the study. Subjects will take 25 g of soy protein daily, while controls will take 25 g of milk protein. Changes in breast density, ER-alpha/ER-beta ratio, and cell proliferation/apoptosis markers will be measured to determine the effectiveness of soy treatment.
During the last decade, new knowledge and technologies have led to recommendations to include breast cancer risk assessment in primary care. Yet, many women still don't know their individual risk, and many physicians haven't integrated risk assessment and discussion into their routine practices largely due to time constraints. Health information technology (IT) tools could provide physicians and patients with novel ways to assess breast cancer risk and educate patients. Celia Kaplan at the University of California, San Francisco will test the efficiency of a tablet, PC-based breast cancer risk education (BCRE) intervention in a primary care setting. Patients enter their health information to produce a personalized risk score, patient BCRE feedback report, and a referring physician report. This should promote discussion between the patient and physician about breast cancer risk and provide recommendations based on solid data. Dr. Kaplan’s team will conduct a randomized controlled trial over 14 months with 800 patients and 97 physicians. The three participating clinics serve a diverse population of African American, Latina, Asian, and Caucasian women.
Etiology & Prevention Grants Listing
Environmental Causes of Breast Cancer Across Generations
Cohn, Barbara Ph.D.
Public Health Institute
Award Type: Program Directed Award
$5,000,000
New Paradigm of Breast Cancer Causation and Prevention
Hiatt, Robert, M.D., Ph.D., M.P.H.
University of California, San Francisco
Award Type: Request for Qualifications
$229,732
Exploring Disparities, Environmental Risk Factors in Teachers
Hurley, Susan, M.P.H. (co-PI)
Reynolds, Peggy, Ph.D. (co-PI)
Northern California Cancer Center
Award Type: Program Directed Award
$132,203
Breast Cancer Risk Reduction: A Patient-Doctor Intervention
Kaplan, Celia, Dr. P.H.
University of California, San Francisco
Award type: Translational research
$740,690
Mammary Gland Evaluation and Risk Assessment
Kushi, Lawrence, Sc.D.
Kaiser Foundation Research Institute
Award type: Joining Forces Conference
$25,000
Model-building with Complex, High-dimensional Exposures
Nelson, David, Ph.D.
Northern California Cancer Center
Award Type: Request for Proposals
$278,195
Cancer Mapping: Making Spatial Models Work for Communities
Roberts, Eric, M.D., Ph.D.
Public Health Institute
Award Type: Request for Proposals
$349,225
Soy Treatment for High-risk Women and DCIS Patients
Wu, Anna, Ph.D.
University of Southern California
Award type: Translational research
$1,217,500
