Improving The Prognosis For Breast Cancer Survival:
Dangerous DNA Damage Can Be Prevented
With Vitamins, Citrus and Soy

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

From Nutrition Science News

By Jack Challem

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Ask women about their greatest health fears, and many will rank breast cancer close to the top, even though they're five times more likely to die from heart disease. Yet conventional medicine, in the quest to prevent breast cancer, has accomplished little more than a dog chasing its own tail. The drug tamoxifen, for instance, helps many women with breast cancer, but they pay the price of an increased risk of endometrial cancer. [1] Medicine would do much better concentrating on genuine prevention--especially through nutrition.

For the past several years, researchers have been trying to unravel the mysteries of the so-called breast cancer genes, named BRCA1 and BRCA2. Women who inherit either of these genes run a 90 percent risk of developing breast cancer. But having these genes isn't necessarily bad. BRCA1 and BRCA2 also control milk production and can be highly advantageous to nursing mothers (e.g., by enabling women to lactate during famines). [2] Furthermore, there's some evidence that properly functioning BRCA1 and BRCA2 genes actually prevent cancer. One study found that normal BRCA1 genes can inhibit tumor growth. [3,4]

Despite all the attention being given to the BRCA1 and BRCA2 genes, only 10 percent of all breast cancers can be linked to them, according to Donald C. Malins, Ph.D., D.Sc., director of molecular epidemiology at the Pacific Northwest Research Foundation in Seattle. Malins, a highly respected researcher, blames most breast cancers on generic free-radical damage to breast cell DNA. Such DNA damage, he says, is likely what makes the BRCA1 and BRCA2 genes turn bad as well.

But, Malins points out, women don't have to passively wait for the damage to occur. [5] "Diets rich in antioxidants that neutralize free radicals may well be helpful at early stages of DNA damage," he says. Later, more powerful and concentrated antioxidants may be necessary to repair the damage, he adds.

One interesting though little-considered marker for breast cancer is catalase. If a person's body fails to produce enough of this important enzyme, the risk of breast cancer--for both males and females--can skyrocket. But the medical profession fails to routinely screen people for it.

Catalase converts hydrogen peroxide into water and oxygen. Without sufficient catalase (or another enzyme called glutathione peroxidase), hydrogen peroxide spins off large numbers of hydroxyl radicals--considered the most dangerous type of free radical.

According to Kunihiko Ishii, M.D., of the Okayama University Medical School, Japan, an estimated 3 million Japanese men and women carry a genetic defect that prevents them from making adequate amounts of catalase. If a comparable (0.23) percent of Americans shared this genetic trait, more than 6 million people in this country would also suffer from low-catalase production. People with insufficient catalase have serious trouble quenching the free radicals that damage their DNA.

In recent experiments, Ishii and his colleagues showed that micewith low or no catalase were especially prone to cancer. He then fed a strain of zero-catalase mice diets either enriched or deficient in vitamin E. He used vitamin E because it is a well-known antioxidant, and some studies have found it protective against breast cancer. [6]

Without vitamin E, the zero-catalase mice had an 82 percent incidence of breast cancer. With vitamin E supplementation, the incidence was only 47 percent. Vitamin E also delayed the onset of breast cancer from 9 to 14 months, or by 35 percent. Aside from demonstrating the protective role of vitamin E in breast cancer, Ishii also showed that serious genetic defects may be partially overcome with supplements.

Unlike many scientists who hesitate to extrapolate animal research to people, Ishii took a very clear stand. He wrote that "vitamin E intrinsically has a protective effect against the development of mammary tumors, and this may apply not only to the ... mouse, but also to humans." [7] So based on Ishii's comments, there is definitely hope for the future.

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The Antitumor Vitamin

There's more good news about vitamin E and breast cancer. A common type of vitamin E supplement, known as vitamin E succinate, has been shown in cell-culture studies and animal experiments to inhibit the growth of various types of cancer. This trait appears unique to vitamin E succinate, which can be identified on bottles by its chemical name "d-alpha tocopherylxx succinate."

Several cell-culture experiments have shown that vitamin E succinate halts the growth of cancerous cells, including breast cancer cells. This form of vitamin E seems to halt cancer cell proliferation by protecting "transforming growth factor-b" that regulates cell growth. [8]

But vitamin E succinate works in other ways as well. In a recent paper, researchers from NCI reported that vitamin E succinate prompts apoptosis (programmed cell death) in breast cancer cells. "An advantage for using vitamin E and/or vitamin E derivatives in human cancer therapy is its low level of toxicity in vivo," wrote Maria C. Birchenall-Roberts, Ph.D., of NCI. [9]

Of course, cell-culture studies are a long way from human trials. But Gerald Shklar, D.D.S., of the Harvard University Dental School, has taken the next step. He used a toxic chemical to induce oral cancer in hamsters, then fed them vitamin E succinate. The vitamin E prevented cancer growth, and its mechanism was particularly surprising. It inhibited angiogenesis (the growth of tumor-feeding blood vessels), thus suggesting yet another way vitamin E may help treat breast cancer. [10]

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Citrus and Genistein Lower Breast Cancer Risk

Fresh fruit juices have occasionally been used as alternative cancer treatments, and a recent series of cell-culture and animal experiments confirms their value. Kenneth K. Carroll, Ph.D., a biochemist at the University of Western Ontario, London, Canada, investigated the effect of orange and grapefruit juices--and some of the nutritional flavonoids they contain--on breast cancer.

He exposed laboratory rats to a cancer-causing chemical, then fed them large amounts of orange and grapefruit juice. The juices slowed the development of breast cancer in the rats. Next, Carroll gave similar rats the flavonoids naringin or naringenin, found in grapefruit juice, and these also slowed the development of breast cancers. Orange juice, containing the flavonoid hesperetin, had a similar beneficial effect.

Carroll also found that hesperetin and naringenin inhibited the proliferation of breast cancer cells in cell-culture experiments. Furthermore, when each of the citrus flavonoids were combined with quercetin, another flavonoid, the combination had a synergistic effect and "suppressed the proliferation of the cells at much lower concentrations than either compound alone." [11]

On another note, researchers have long known that Asian women, who eat large amounts of soy foods, have a relatively low risk of breast cancer. Their risk of breast cancer, however, increases when they move to the United States and begin eating low-soy diets.

Soy foods contain a particular group of flavonoids, called isoflavones, that have very weak estrogenic activity. One of these isoflavones, genistein, has only 1/1000th the hormonal activity of true estrogen. What happens, researchers believe, is that genistein competes directly against estrogen for cell receptors and can block the more powerful estrogen, which is known to increase cancer risk.

Based on animal experiments, a woman who begins eating soy foods as a child might have a lower risk of breast cancer as an adult. Coral A. Lamartiniere, Ph.D., a researcher at the University of Alabama, Birmingham, added either genistein or a placebo to the diets of prepubescent laboratory rats. Later, she exposed all of the rats to a cancer-causing chemical.

The animals given genistein developed almost 50 percent fewer mammary tumors during their lifetimes compared with those given the placebo, according to Lamartiniere's article in Carcinogenesis. They also had slightly longer menstrual cycles, a factor which is also associated with lower breast cancer risk in women. [12]

Although genistein modulates the effects of estrogen, it may reduce the risk of breast cancers in still other ways. For example, genistein inhibits tyrosine protein kinase, an enzyme that promotes cancer cell proliferation. It also blocks angiogenesis and induces cancer cell death. [13] Genistein is a potent antioxidant--more powerful than other isoflavones--and, as discussed above, dietary antioxidants are strongly associated with cancer prevention. [14] In addition, genistein stimulates the body's production of its own antioxidant enzymes, including glutathione peroxidase, catalase and superoxide dismutase (SOD). [15]

What all of this research shows is that common nutrients, in concentrated form, can prevent many types of DNA damage that lead to cancer. [16] In practical terms, this means women don't have to wait in fear of breast cancer, or hope for the distant promise of high-tech and high-priced gene therapy. Nutritional supplements qualify as a form of natural gene therapy that women can use today to protect the genes they were born with.

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Jack Challem, based in Aloha, Ore., has been writing about vitamin research for more than 20 years and publishes The Nutrition Reporter newsletter.

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REFERENCES

1. Daniel, Y., Inbar, M., Bar-Am, A., et al. "The effects of tamoxifen treatment on the endometrium." Fertility and Sterility, 65: 1083-89, 1996. 2. Kolata, G. "Seeking reasons for disease genes." New York Times, Dec. 3, 1996: B5. 3. Jensen, R.A., Thompson, M.E., Jetton, T.L., et al. "BRCA1 is secreted and exhibits properties of a granin." Nature Genetics, 12: 303-08, 1996. 4. Travis, J. "Breasts may secrete tumor suppressor." Science News, 149: 132, March 2, 1996. 5. Malins, D.C., Polissar, N.L., et al. "Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation." Proceedings of the National Academy of Sciences of the USA, 93: 14047-52, Nov 26, 1996. 6. Kimmick G.G., Bell R.A., & Bostick, R.M. "Vitamin E and breast cancer: A review." Nutrition & Cancer, 27: 109-17, 1997. 7. Ishii, K., Zhen, L.X., et al. "Prevention of mammary tumorigenesis in acatalesemic mice by vitamin E supplementation." Japanese Journal of Cancer, 87: 680-84, 1996. 8. Charpentier, A., Simmons-Menchaca, M., et al. "RRR-a-tocopheryl succinate enhances TGF-b1, -b2, and -b3 TGF-bR-II expression by human MDA-MB-435 breast cancer cells." Nutrition & Cancer, 26: 237-50, 1996. 9. Turley, J.M., Fu, T., et al. "Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor-negative human breast cancer cells." Cancer Research, 57: 881-90, March 1, 1997. 10. Shklar, G., & Schwartz, J.L. "Vitamin E inhibits experimental carcinogenesis and tumour angiogenesis." Oral Oncology, European Journal of Cancer, 32B: 114-19, 1996. 11. So, F.V., Guthrie, N., et al. "Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices." Nutrition & Cancer, 26: 167-81, 1996. 12. Murrill, W.B., Brown, N.M., et al. "Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats." Carcinogenesis, 17: 1451-57, July 1996. 13. Barnes, S., Peterson, G., et al. "Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer." Journal of Cellular Biochemistry, 22S: 181-87, 1996. 14. Ruiz-Larrea, M.B., Mohan, A.R., et al. "Antioxidant activity of phytoestrogenic isoflavones." Free Radical Research, 26: 63-70, 1997. 15. Cai, Q., & Wei, H. "Effect of dietary genistein on antioxidant enzyme activities in SENCAR mice." Nutrition and Cancer, 25: 1-7, 1996. 16. Wei, H., Cai, Q., et al. "Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein." Carcinogenesis, 17: 73-77, 1996.

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