Prevention: Ending the Danger
Prevention: Ending the Danger Prevention is the ultimate solution to the breast cancer crisis, however, our lack of understanding of what actually causes breast cancer hampers the development of effective prevention strategies. Nevertheless, BCRP-funded researchers are using several plausible theories about causes of breast cancer to devise new ways to prevent the disease:
Diet and Other Active Lifestyle Modification: What Women Can Do Now. Because our diet is something we can change, many of the studies we fund explore the components of the diet that increase or decrease the risk of breast cancer.
Safer Preventive Drugs: Investigating Naturally Occurring Compounds. The chemotherapy drugs currently available for prevention do not have ideal risk/benefit ratios. BCRP studies investigate compounds from food that show potential for preventing breast cancer.
Hormones or Environmental Contamination Interacting with Known Risk Factors. The connection between environmental contaminants and breast cancer is difficult to prove, because the interactions between cancer-causing substances in the environment and breast tissue are complex. Our studies are designed to investigate those complex interactions, identify those most susceptible to cancer-causing environmental substances and devise prevention methods.
Research Conclusions Research in Progress Research Initiated in 2000 |
Research Conclusions
Diet and Other Active Lifestyle Modification: What Women Can Do Now
Alteration of Dietary Fat to Reduce Breast Cancer Metastasis
Previous studies with human cell lines have indicated that some types of dietary fat can decrease the ability of breast tumors to grow or spread to other parts of the body. Kent L. Erickson, Ph.D., of the University of California, Davis looked for the mechanism behind this effect. He asked, does fish oil with n-3 fatty acid (found in most fish, with higher levels in salmon, tuna and lake trout) decrease breast tumors' ability to stimulate blood vessel growth? And does it decrease the level of specific proteins tumors need to grow and spread? The answer is yes to both questions. Dr. Erickson's results indicated that fish oils may decrease tumor cells' ability to lodge in the lung. Fish oil decreases the number of macrophages, a type of white blood cell, in breast tumors. Macrophages produce a specific protein that tumors appear to need to make their blood vessels grow. Decreasing a tumor's ability to grow blood vessels appears to limit the tumor's ability to grow and spread. Dr. Erickson also found that tumors produce a unique enzyme necessary for blood vessel growth. The enzyme increases in animals fed safflower diets and is inhibited in animals fed fish oil diets. This research strengthens the theory that altering dietary fat can be used as an additional therapy at any stage of breast cancer.
Safer Preventive Drugs: Investigating Naturally Occurring Compounds
Analogs of Tea Polyphenols for Breast Cancer Chemoprevention
Previous reserach has suggested that a compound in green tea, epigallocatechin-3-gallate (EGCG), could potentially be used to prevent or treat cancer. However, to get a therapeutic effect, a woman would need to drink 8-10 cups of green tea per day. Nurulain Zaveri, Ph.D., of SRI International, Menlo Park modified the complex chemical structure of EGCG to derive similar, more potent compounds. The lead compound, SR 13197, attacks tumors by killing the inner cells of tumor blood vessels, thus decreasing the tumor's blood supply. BCRP is funding Dr. Zaveri over the coming year to further develop compounds derived from EGCG.
Research in Progress
Safer Preventive Drugs: Investigating Naturally Occurring Compounds
Breast Cancer Prevention with Phytoestrogens in Grape Juice. Shiuan Chen, Ph.D., at the Beckman Research Institute, City of Hope, Duarte is testing compounds isolated from red grape juice for their ability to prevent tumor formation in animal cell lines. He is also investigating whether these red grape juice-derived compounds inhibit aromatase, an enzyme that generates estrogen. His work is aimed toward discovering whether the most potent grape juice-derived compounds will either prevent cancer cells from forming, or eradicate them once they form, or both. The goals include a possible preventive medication for post-menopausal women.
Dietary Indole Analogs for Breast Cancer Prevention. Indole-3-carbinol--found in cruciferous vegetables, such as cabbage, broccoli, and brussels sprouts--is a promising breast cancer preventive. Ling Jong, Ph.D., at SRI International, Menlo Park has varied the structure of one of the major forms of Indole-3-carbinol that is active in the digestive tract. She tested the resulting compounds in a breast cancer cell line for anti-tumor activity. Two compounds showed the highest anti-tumor activity. Dr. Jong will test them in animal models over the coming year.
Diet and Other Active Lifestyle Modification: What Women Can Do Now
Diet & Breast Cancer in the California Teachers Study Cohort. Pamela Horn-Ross, Ph.D., of the Northern California Cancer Center, Union City is analyzing data on the diets of women who are part of the California Teachers Study. This statewide study is following a large group of teachers over time, tracking which women develop cancer, and gathering other information about the women's lives. Preliminary analysis suggests that the diet over the previous year may not influence the development of breast cancer. However, Dr. Horn-Ross needs to complete substantial additional analyses of the data during 2001.
Research Initiated in 2000
Diet and Other Active Lifestyle Modification: What Women Can Do Now
Bovine Leukemia Virus Infection and Human Breast Cancer Risk. Gertrude Buehring, Ph.D., at the University of California, Berkeley has previously shown that a majority of women have antibodies to bovine leukemia virus. This virus is found in beef and milk and can be transmitted to humans. It causes mammary tumors in animals. The antibodies in women may be a response to a live virus, or to a harmless, de-activated part of the virus, and it isn't possible to determine which through laboratory testing. Therefore, Dr. Buehring will begin to test the speculative hypothesis that bovine leukemia virus is associated with an increased risk of breast cancer. She is using a case-control study of 338 women to see if women with breast cancer are more likely to have the virus in their breast tissue than women with no history of breast cancer.
Safer Preventive Drugs: Investigating Naturally Occurring Compounds
Mechanisms of Reduced Metastasis by Conjugated Linoleic Acid. Conjugated linoleic acid is a naturally-occurring compound found in some sources of dietary fat, including beef and dairy products. In small amounts, it has been shown to reduce the spread of mammary cancer in mice. Kent L. Erickson, Ph.D., of the University of California, Davis is investigating how conjugated linoleic acid can reduce a tumor's ability to form blood vessels it needs in order to grow. He is also investigating how conjugated linoleic acid reduces a tumor's ability to make compounds that enable tumor cells to travel and take root in other parts of the body.
Breast Cancer Prevention by Analogs of EGCG from Green Tea. Nurulain Zaveri, Ph.D., at SRI International, Menlo Park is building on previous successful BCRP-funded research to improve the breast cancer preventive action of a compound found in green tea, epigallocatechin-3-gallate (EGCG). She will test individual components of EGCG for their ability to inhibit cell growth in a breast cancer cell line. Next, she will modify the most active components to make them more potent or to introduce characteristics that make the modified components easier for the body to absorb and use. The eventual goal is a medication that will be more effective, and have fewer side effects, than the current breast cancer prevention drug, tamoxifen.
How Hormones or Environmental Contaminants Interact with Known Risk Factors
Upregulation of BRCA1 as a Cancer Preventive Strategy. Abnormal BRCA1 genes predispose women to breast cancer. In theory, the normal BRCA1 gene produces a protein that makes cells resistant to cancer. Donna Williams-Hill, Ph.D., of the University of Southern California, Los Angeles is investigating how altering the levels of hormones surrounding the normal BRCA1 gene affects the gene's ability to produce this protein. She is altering hormone levels in female rats, measuring the level of protein produced by the BRCA1 gene, then determining how much mammary cancer the cells develop under the varying hormonal conditions. She will also analyze normal and cancerous human breast tissue (obtained under another BCRP-funded study) for levels of BRCA1-produced protein.
Genetic and Environmental Modifiers of Breast Cancer Risk. Argyrios Ziogas, Ph.D., of the University of California, Irvine, will investigate how two types of genes interact to raise or lower breast cancer risk. The first type of genes are BRCA1 and BRCA2, on which abnormalities are already known to increase a woman's risk of breast cancer. The second type of gene interacts with cancer-causing chemicals in the environment and may elevate breast cancer risk. Dr. Ziogas will use data from the unique resource of a breast and ovarian cancer registry of 1,176 families, a questionnaire providing environmental exposure and lifestyle information, and analysis of the families' genes. Results should add to our understanding of the BRCA genes' role in breast cancer, and of interactions between BRCA genes and genes that interact with environmental contaminants. This could lead to improved individualized risk prediction, and targeted preventive strategies.
Mammographic Density, HRT and Hormonal Activity Genes. Women whose breast tissue appears denser than average on a mammogram have a higher risk of breast cancer. Thomas Mack, Ph.D., of University of Southern California, Los Angeles is investigating whether density of breasts is inherited and how certain hormones affect breast density. Dr. Mack's team will compare the breast density of identical twins who are taking various kinds of hormone replacement therapy. After adjusting for any other pertinent characteristics, they will determine if the hormones are causing any difference in breast density. The team will also investigate how estrogen metabolism genes influence breast density. They will do this by comparing breast density among sets of identical twins (who have identical estrogen metabolism genes) and fraternal twins (who are more likely to have different estrogen metabolism genes).
