Prevention and Risk Reduction:
Ending the Danger of Breast Cancer

According to current science, only about one in ten cases of breast cancer is due to inherited abnormal genes. The other nine are caused by environment and lifestyle, or by interactions between genes and environment and lifestyle. So changing women’s environment or lifestyle has great potential to prevent cancer; however, the question is: which changes should be made? The CBCRP funds research into promising areas, including diet and behaviors that women can change to reduce their risk, and new prevention strategies. We also encourage studies on tests that can predict the likelihood of a woman getting breast cancer or measure if attempts at prevention are reducing her risk, and on groups of women who have genes that may raise their risk for breast cancer.

Research Conclusions

Four CBCRP grants examining Prevention and Risk Reduction options in breast cancer were completed in 2003.

Bovine Leukemia Virus Infection and Human Breast Cancer Risk.
Gertrude Buehring, Ph.D., at the University of California, Berkeley, investigated whether being infected with the bovine leukemia virus can increase a woman’s risk for breast cancer. She had previously shown that a majority of women have antibodies to bovine leukemia virus. The virus is found in beef and milk; it can be transmitted to humans who eat non-pasteurized dairy products or undercooked beef. It causes mammary tumors in animals (the equivalent of breast tumors in humans). The research team analyzed samples of normal breast tissue and breast tumors. The tumor tissue had a higher rate of infection with bovine leukemia virus than the normal tissue, but the team was not able to test enough tissue samples for the results to be statistically significant. Results of the study were published in AIDS Research and Human Retroviruses 18(12): 1105-1113. Dr. Buehring plans to continue this research.

Breast Cancer Prevention with Phytoestrogens from Grape Juice.
Grape juice suppresses breast cancer cell growth by preventing the synthesis of the female hormone estrogen. About 60 percent of breast tumors in premenopausal women and 75 percent of those in post-menopausal women depend on estrogen for growth. This suggests that drinking grape juice may reduce the risk of breast cancer. Shiuan Chen, Ph.D., at the Beckman Research Institute, City of Hope, Duarte, isolated and tested compounds from grape juice and red wine for their ability to prevent tumor formation. Grape juice extracts were difficult to isolate because of the sugar in the juice, so the team turned to red wine extracts. They found that a red wine extract containing compounds known as procyanidin B dimers (which are present in grape seeds) completely stops the action of aromatase, an enzyme that generates estrogen in cells. The extract stopped the growth of tumor cells in laboratory cultures. When the extract was fed to mice genetically engineered to produce extra aromatase, it prevented tumors and the mice also exhibited other signs of estrogen deprivation. Results of the study were published in Cancer research 2003 Dec 1; 63:8516-8522.

Evaluation of Essiac Tea to Prevent Mammary Tumors.
Essiac tea, an herbal mixture introduced in the 1920s to treat cancer, is commonly used today by breast cancer survivors to try to prevent recurrence. Many of the herbs used in Essiac tea have biological activities associated with decreasing cancer risk and long histories of use in Asian diets and medicine; yet there have been no previous published scientific studies evaluating Essiac tea’s effectiveness at preventing breast cancer. Kristen S. Kulp, Ph.D., of the Lawrence Livermore National Laboratory, fed one group of rats with water and another with a 3 percent solution of an Essiac herbal tonic. All rats were then exposed to the same cancer-causing substance. Eighty-two percent of the rats fed the Essiac tonic had mammary tumors, which are the equivalent of breast tumors in humans, compared to 71 percent of those fed water. The rats fed Essiac also had twice as many tumors. The team then tested Essiac tea on rats whose genes had been altered to cause the mice to spontaneously form mammary tumors that are the equivalent of Her-2/Neu-positive breast tumors in humans. These tumors are among the most likely to spread to other parts of the body and cause death. The mice fed Essiac tea had fewer tumors than the mice that did not receive any. However, the mice fed Essiac tea did not live as long as the others. The results suggest that in some instances, Essiac tea may protect against breast cancer, and in others, promote the disease. The CBCRP is funding further research into Essiac tea.

Breast Cancer Prevention by Analogs of EGCG from Green Tea.
Nurulain Zaveri, Ph.D., at SRI International, Menlo Park, built on previous successful CBCRP-funded research to improve the breast cancer preventive action of a compound found in green tea, epigallocatechin-3-gallate (EGCG). Because of the way EGCG is absorbed and digested in the body, a woman has to drink 8–10 cups of green tea per day to get a preventive effect. Since each cup contains 70 mg. of caffeine, drinking large amounts of green tea leads to caffeine-related side effects. Dr. Zaveri has synthesized a chemically-modified version of EGCG that is five times more powerful at inhibiting the growth of breast cancer cells. It works both against breast cancer cells that need estrogen for survival and those that do not. This EGCG analog can also be absorbed by the digestive tract more easily than the EGCG found in green tea. Dr. Zaveri plans to test the new compound further with a goal of developing a pill that could be taken by women who are at high risk for their breast cancer recurring. Results of the study were published in Synthesis 2 (2003):267-71 and Organic Letters 2001 Mar 22; 3(6):843-6.

Research in Progress

Breast Cancer Prevention with Estrogen.
Having a baby before age 20 protects a woman from breast cancer. Satyabrata Nandi, Ph.D., at the University of California, Berkeley, treated mice and rats with a 7–21 day hormone treatment with levels of estrogen comparable to those during pregnancy. Those mice and rats, along with mice and rats that hadn’t had the hormone treatment, were then given a cancer-causing substance, to see if the hormone treatment provided protection from mammary cancer (the mouse/rat equivalent of breast cancer). The rodents with the hormone treatment had 80 percent less cancer. This nontoxic treatment is as effective at preventing mammary cancer as a full-term pregnancy, removal of the ovaries, or long term treatment with the preventive drug tamoxifen. The research team also found that the hormone treatment caused genes involved in growth promotion to become less active, and genes involved in growth inhibition to become more active.

Research Initiated in 2003

Four grants studying prevention and risk-reduction options began in 2003.

Preventing Breast Cancer with Ginseng.
Michael DeGregorio, Ph.D., at the University of California, Davis, is investigating whether ginseng, a natural remedy used for thousands of years in Asia, can prevent breast cancer. He is giving three groups of mice a chemical that causes breast cancer. Some mice will then get ginseng, others a drug that prevents breast cancer, and others no treatment. The research team will then compare the number and type of tumors in all three groups of mice.

Studying the Interaction of an Essiac Tea and a Food Mutagen.
Women who eat well-done meat have a higher risk of breast cancer than those who don’t. PhIP is a chemical formed when meat is cooked; it damages DNA in cells and causes breast tumors in rats. Essiac tea is an herbal mixture women with breast cancer often use in addition to treatment prescribed by a physician. Kristen Kulp, Ph.D., at Lawrence Livermore National Laboratory, is investigating whether Essiac tea protects cells against DNA damage and tumors caused by PhIP.

Common Genetic Variation & Breast Cancer: A Genomic Approach.
Women who have mutations in certain genes have a higher than average risk for breast cancer. Christopher Haiman, Ph.D., at the University of Southern California, Los Angeles, is investigating whether some versions of these genes that are considered normal also raise the risk for breast cancer. The research team will study hundreds of subtle differences in the genes of a large group of African American, Latina, Japanese, white, and Hawaiian women in Los Angeles and Hawaii.

The IGF Pathway and Breast Cancer Risk in African Americans.
African American women under age 50 are twice as likely to die from breast cancer as white women from the same age group. Susan Neuhausen, Ph.D., at the University of California, Irvine, is investigating a group of genes called the IGF pathway, which may directly affect cell growth. She will compare the IFG pathway genes in 600 African American women with breast cancer and 232 African American women without the disease to see if there are any differences.