Etiology and Prevention
What in the environment—interacting with what unique aspects of each woman’s body—alters her risk of developing breast cancer? Despite efforts that have identified genes that greatly increase breast cancer risk and many studies on environmental causes, the disease strikes most women seemingly at random. The CBCRP encourages new California-based studies to understand the environmental causes of breast cancer, and how these increase risk and impact different communities of California women.
Research Conclusions
Migration and Breast Cancer Risk in Hispanics.
When women migrate from Latin American countries, where the risk of breast cancer is low, to the U.S., where the risk is higher, they become more likely to get the disease. Esther John, Ph.D., of the Northern California Cancer Center, Union City, investigated why this happens. Her research team compared over 1,100 Hispanic women with breast cancer to over 1,400 Hispanic women who didn’t have the disease. They found that a third-generation Hispanic woman was six times more likely to get breast cancer than a Hispanic woman who recently moved to the U.S. Women who still used Spanish as their primary language were less likely to get breast cancer, even if they had been in the U.S. a long time. Changing from Spanish to English is a measure of how much, or little, these women have adopted U.S. culture. U.S.-born Hispanic women were more likely than recent arrivals to use alcohol and hormone replacement therapy. They were less likely to begin menstruation at a higher age, have a baby at a young age, and to breastfeed. These factors explained most of the difference in the breast cancer rates among pre-menopausal, but not post-menopausal, Hispanic women. Their data suggests that changes in hormonal and lifestyle factors associated with living in Western countries like the U.S. have a major influence on the development of breast cancer. Therefore, the identification and communication of risk factors that can be modified (i.e., breast feeding, physical activity, body weight, alcohol consumption, diet) is important in reducing breast cancer risk.
Pesticides and Breast Cancer in Hispanic Women in California.
Paul K. Mills, Ph.D., at the Public Health Institute, Berkeley, investigated whether exposure to two classes of commonly-used pesticides, organochlorines and triazines increases Hispanic California women’s risk for breast cancer. The research team approached the question in two ways. First, they compared the breast cancer rate among Hispanic women with pounds of pesticide used, for each of California’s 58 counties during the years 1988–1999. In line with previous research, older and higher-income Hispanic women had higher breast cancer rates, and those with more children had lower rates. The risk of cancer among Hispanic women was also 18% higher in counties with the highest use of the organochlorine insecticide methoxychlor and 16% higher for another organochlorine pesticide, toxaphene. High use of triazine pesticides did not raise the risk for breast cancer. The second approach the researchers used was to evaluate the breast cancer risk among women members of the United Farm Workers of America
union. Their risk of breast cancer was not related to any specific crop, except mushrooms, where a small subgroup faced a risk six times higher than women who didn’t work with this crop. Breast cancer risk was also not associated with the women working with specific chemicals. However, the more the women worked with all the pesticides covered in this study combined, the higher their risk, until the women with the most exposure to all pesticides had a risk 41% higher than those with the least. Risk of breast cancer associated with pesticide use was stronger in young women.
4th International Symposium on the Intraductal Approach to the Breast.
The Dr. Susan Love Research Foundation, Pacific Palisades, held its fourth conference to develop a new model for detecting and preventing breast cancer. Accessing the lining of the milk ducts in the breast, where cancer starts, could be the basis for a test much like the Pap smear for cervical cancer. This conference brought together over 100 researchers, clinicians, and patient advocates from California, the U.S., and the world. The researchers brought a variety of scientific backgrounds, including medical oncology, internal medicine, surgery, radiology, biochemistry, pathology, endocrinology, epidemiology, and biostatistics. Participants shared research findings, developed multi-disciplinary collaborations, and awarded seven pilot grants to stimulate new research. A panel provided the public with an opportunity to learn about the intraductal approach and to ask questions about current breast cancer treatment options.
Breast Cancer Prevention with Phytochemicals in Mushrooms.
Higher levels of the enzyme aromatase in breast tissue raise a woman’s risk for breast cancer. Drugs that inhibit aromatase are effective in treating breast cancer that depends on hormones, and may also have the potential to prevent breast cancer in post-menopausal women. Shiuan Chen, Ph.D., at the Beckman Research Institute, City of Hope, Duarte, found that an extract from white mushrooms inhibits aromatase in one type of breast tumor cells growing in culture. These breast tumor cells were dependent on estrogen, high in aromatase, and proliferated when exposed to the hormone testosterone. When fed to animals with tumors that had the same characteristics as the tumor cells in culture, the mushroom extract also slowed down tumor growth. The extract works not by killing cancer cells, but by preventing aromatase from allowing tumor growth. More than one chemical in the mushrooms extract may inhibit aromatase. This study suggests that post-menopausal women can benefit from a diet that includes mushrooms.
Mechanisms of Reduced Metastasis by Conjugated Linoleic Acid.
Conjugated linoleic acid is found in some sources of dietary fat. Kent Erickson, Ph.D., at the University of California, Davis, found prior to this study that conjugated linoleic acid can be a potent protective against mammary tumors in mice, the equivalent of breast cancer in humans. In this study, he found that feeding mice diets that included conjugated linoleic acid lowered the levels of proteins in their tissues that cause tumors to form, compared to mice fed similar diets without conjugated linoleic acid. Tumors took a longer time to establish in mice fed conjugated linoleic acid. When mice fed conjugated linoleic acid had tumor cells injected into their blood, fewer tumors grew. When conjugated linoleic acid is applied directly to tumor cells growing in a lab culture, it kills them. Conjugated linoleic acid also alters the ability of tumor cells to invade and migrate,
and it changes the action of several genes involved in tumor initiation, growth and spread. These findings add to accumulating evidence that conjugated linoleic acid may be an important preventive agent for breast cancer.
Upregulation of BRCA1 as a Cancer Preventive Strategy.
Donna Williams-Hill, Ph.D., and Colin K. Hill, Ph.D., at University of Southern California, Los Angeles, investigated how two genes, BRCA1 and BRCA2, interact with hormones in the breast. The normal versions of these genes suppress tumors by producing proteins, also caused BRCA1 and BRCA2. A small percentage of women have mutated versions of either or both these genes that fail to suppress tumors and make the women more prone to breast cancer. The research team found that in rats, levels of BRCA1 protein rise at puberty. A strain of rats bred to be susceptible to breast cancer had much lower levels of BRCA1 protein than rats bred to be resistant. The team also found strong evidence that fluctuations in hormone levels that occur when the rats go through the estrus cycle control the level of BRCA1 and 2 in cells. Rats exposed to radiation at a time when their levels of BRCA1 protein were high got fewer tumors than rats exposed when their BRCA1 protein levels were low. The team is doing further research to find out whether changing the rats’ hormones artificially produces a change in the level of BRCA1 protein.
Genetic and Environmental Modifiers of Breast Cancer Risk.
Women with a family history of breast cancer have a higher than average risk of getting the disease. Only 15–20% of familial breast cancer is accounted for by two breast cancer susceptibility genes, BRCA1 and BRCA2. Argyrios Ziogas, Ph.D., at the University of California, Irvine, investigated how several genes that are involved in the metabolism of the hormone estrogen or of cancer-causing substances from the environment may be associated with breast cancer. The research team found that taking the hormone progesterone raises the breast cancer risk of women who have certain variations of two genes, COMT and CYP1A1. Women with a variation of another gene, GSTM, raise their risk for breast cancer if they take oral contraceptives. Lower weight at age 18 raises the risk for breast cancer of women with certain variations of the CYPA1A gene. The MM variation of the GSTT gene raises a woman’s risk for breast cancer. None of the genes studied made a woman’s breast cancer risk higher if she smoked. The researchers also found that 1.3% of women have the cancer-prone version of the BRCA1 gene, and 1.9% have the cancer-prone version of BRCA2. Results of this study will help improve individualized risk prediction and preventive strategies.
Using Microarrays to Estimate Breast Cancer Risk.
Exposure to X-rays is linked to developing breast cancer. Bradley Ekstrand, M.D., Ph.D., at Stanford University, attempted to find out if the development of breast cancer is related to an abnormal genetic response to X-rays. He obtained blood samples from 41 women who had long ago received radiation to the chest as part of their treatment for Hodgkin’s disease. Nineteen of these women had since developed breast cancer. Dr. Ekstrand exposed all the blood samples to radiation. Using microarrays, a technology that allows researchers to search for thousands of genes at a time, Dr. Ekstrand attempted to find genetic differences in the way blood cells from women who’d had breast cancer
handled radiation, compared to blood cells from women who hadn’t had the disease. He couldn’t find any significant differences, but other researchers at this lab are continuing to pursue this question.
Prolactin and Breast Cancer Risk in a Multiethnic Cohort.
The hormone prolactin circulates in the blood. It is important to breast development during puberty and pregnancy, and to milk production. Women with higher levels of prolactin the their blood may have a higher risk for breast cancer. Brian Henderson, M.D., at the Keck School of Medicine, University of Southern California, investigated whether genes control the levels of prolactin in the blood. He tested blood samples from African American, Hawaiian, Japanese, Latina, and white women who had breast cancer and women from the same ethnic groups who did not. One variation on the prolactin gene (SNP 35 [intron 1] in the region of low linkage disequilibrium) was associated with higher prolactin levels in the blood. However, there was no relationship between breast cancer risk and any variations of the prolactin gene or of the gene that produces a protein that allows cells to take in prolactin.
Physical Activity and Diet in Adolescents with Disabilities.
A number of research studies suggest that physical activity and nutrition may be associated with the risk of breast cancer. However, this research has not been targeted to women with disabilities. Carol Koprowski, Ph.D., R.D., and Katherine Hall, Ph.D., at California State University, Northridge, attempted to study the feasibility of developing appropriate assessment tools to measure physical activity and dietary intake in teenage girls with disabilities. The researchers held focus groups where teenage girls with disabilities discussed their views on current dietary and physical activity recommendations. However, the research team was not able to get permission from schools and parents to interview enough teenage girls to complete the research.
Grants in Progress: 2005
| TOP ^ |
Serpentinites & the High Incidence of Breast Cancer in Marin
Janice Barlow and Scott Fendoff
Marin Breast Cancer Watch and Stanford University
Surrogate Markers for Green Tea
Mai Brooks and Jian Rao
University of California, Los Angeles
Genetics, Obesity, and Breast Cancer Risk
Catherine Carpenter
University of California, Irvine
Assessing Recurrent Genomic Aberrations Linked to Ethnicity
Koie Chin
University of California, San Francisco
The Hygiene Hypothesis and Breast Cancer Risk
Christina Clarke
Northern California Cancer Center
| TOP ^ |
Can Placenta Factors Explain Race Patterns in Breast Cancer?
Barbara A. Cohn
Public Health Institute
Preventing Breast Cancer with Ginseng
Michael DeGregorio
University of California, Davis
Epstein-Barr Virus in Breast Cancer Tissues
Sally Glaser
Northern California Cancer Center
Immune-Function Genes and Race Differences in Breast Cancer
Sally Glaser
Northern California Cancer Center
Common Genetic Variation & Breast Cancer: A Genomic Approach
Christopher Haiman
University of Southern California
Dietary Fat, Fat Metabolizing Genes, and Breast Cancer Risk
Sue Ann Ingles
University of Southern California
Control of Aromatase Expression in Breast Cancer
Ikuku Kijima
Beckman Research Institute of the City of Hope
Studying the Interaction of an Essiac Tea and a Food Mutagen
Kristen Kulp
Lawrence Livermore National Laboratory
Breast Cancer Chemoprevention with Dietary Herbal Estrogens
Dale Leitman
University of California, San Francisco
Breast Cancer Prevention with Estrogen
Satyabrata Nandi
University of California, Berkeley
The IGF Pathway and Breast Cancer Risk in African Americans
Susan Neuhausen
University of California, Irvine
PDDEs in Tissues of Women With and Without Breast Cancer
Myrto Petreas
California Department of Health Services
| TOP ^ |
HER-2/neu Gene Variations and Breast Cancer Risk
Michael Press
University of Southern California
Birth Characteristics and Breast Cancer in Young Women
Peggy Reynolds
California Department of Health Services
USC/NCCC Breast Cancer Research Training Program
Ronald K. Ross
University of Southern California
Estrogen Metabolizing Genes, Soy and Breast Cancer in Asians
Anna Wu
University of Southern California
Tea, Genes, and Their Interactions on Breast Cancer
Anna Wu
University of Southern California
Lifestyle Factors and Breast Cancer Prognosis in Asian Americans
Anna H. Wu
University of Southern California
Research Initiated in 2005
| TOP ^ |
Targeted Chemoprevention in a Mouse Model for DCIS
Jeffrey P. Gregg.
University of California, Davis
Structural Characterization of Aromatase
Yanyan Hong.
Beckman Research Institute of the City of Hope
Estrogen Receptor Beta Agonists to Prevent Breast Cancer
Peter J. Kushner
University of California, San Francisco
Breast Cancer Risk Profile of Vietnamese Nail Salon Workers
Kim D. Nguyen and Peggy Reynolds
Asian Health Services and Impact Assessment, Inc.
Grape Seed as a Natural Breast Cancer Chemopreventive Agent
Melanie Ruth Palomares
Beckman Research Institute of the City of Hope
Breast Cancer Lymphedema: Role of Insulin Resistance/FOXC2
Stanley G. Rockson
Stanford University
Breast Cancer Risk Associated with High Mammographic Density
Thea D. Tlsty.
University of California, San Francisco
| TOP ^ |
Androgen Receptor Gene and p21 Gene in Breast Cancer
Wei Wang
University of Southern California
