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Breast Cancer Prevention

by Hans R. Larsen, MSc ChE

Vitamin D and breast cancer
Hans Larsen SAN DIEGO, CA. A report has just appeared in the Journal of Steroid Biochemistry & Molecular Biology by Garland et al that addresses the issue of vitamin D and breast cancer risk with a pooled analysis of studies that determined the vitamin D status from serum 25-hydroxyvitamin D (25(OH)D) levels. The list of authors includes both well-known vitamin D experts and nutritional epidemiologists. The authors were only able to find two studies that met their requirements for inclusion in their pooled analysis, but together they involved 1760 individuals. Both studies covered a wide range of 25(OH)D levels and exhibited a high level of inverse correlation between breast cancer risk and the serum level of this vitamin D marker. When pooled analysis was carried out, the odds ratios for the lowest to highest quintile of 25(OH)D levels were 1.00, 0.90, 0.70, 0.70 and 0.50, i.e. the highest vitamin D status provided a 50% reduction in risk. The authors present a graph of risk (odds ratio) against serum 25(OH)D levels with an amazing correlation coefficient of 0.94 (a statistical measure of the goodness of fit to the model, in this case a straight line, and 1.00 represents a perfect fit), a correlation coefficient that would please those trained in the physical sciences and in fact a correlation very rarely seen in plots presented in the medical literature.

The authors discuss the level of intake that would accomplish the 50% level of risk reduction. If a person were to start at a serum level of 24 nmol/L (10 ng/mL) it would require supplementation of 4000 IU/day to achieve the required level of 120 nmol/L. This exceeds the current upper limit of 2000 IU/day. However, as they point out, a proposal has been made to raise this limit to 4000 IU/day. Levels of 24 nmol/L are not uncommon among US women in the winter months. An alternative they explore is to take 2000 IU/day orally and make up the balance by judicious sun exposure. They estimate that 12 minutes of sun exposure for 50% of the skin would produce the missing 2000 IU. However, this would not happen in the northern latitudes in the winter months. The authors hammer home their point regarding the importance of vitamin D by calculating that, based on their data, an intake of 4000 IU of vitamin D per day would, in the U.S., prevent over 100,000 cases of breast cancer per year. Intake of 2000 IU/day was estimated to prevent 66,000 cases. In this paper, vitamin D refers to vitamin D3.
Garland, C. F. et al. Vitamin D and the Prevention of Breast Cancer; Pooled Analysis. Journal of Steroid Biochemistry & Molecular Biology, 2007, Vol. 103, pp. 708-711.

Vitamin D, breast and ovarian cancer
LONDON, UK. Exposure to solar ultraviolet B radiation (UVB) has been found to correlate with age-adjusted incidence of ovarian cancer in a study involving 175 countries and based on data from 2002. Not only was an inverse relationship found, but when the correlation with stratospheric ozone, which reduces UBV, was examined, a positive association was found consistent. These results are consistent with earlier studies that found a north-south gradient for age-adjusted mortality rates for ovarian cancer. In another recent study, serum levels of the vitamin D metabolite, 25-hydroxyvitamin D, were measured prospectively in 279 Caucasian women with invasive breast cancer, 204 of which had early stage cancer and 75 of which had locally advanced or metastatic disease. Patients with early stage disease had significantly higher circulating levels of 25-hydroxyvitamin D than those with advanced disease. The authors suggest that these results lend weight to the hypothesis that the growth of breast cancer in vivo is inhibited by vitamin D.
Garland, C.F. et al. Role of Ultraviolet B Irradiance and Vitamin D in Prevention of Ovarian Cancer. American Journal of Preventive Medicine., 2006y, Vol 31, No. 6, pp. 512-14.
Palmieri, C. Serum 25-Hydroxyvitamin D Levels in Early and Advanced Breast Cancer. Journal of Clinical Pathology, 2006, published on line ahead of print.

Olive oil helps combat breast cancer
There is ample evidence that the diet consumed in Mediterranean countries helps protect women against breast cancer. Now Professor Javier Menendez and his team at Northwestern University in Chicago suggest that olive oil may be the main protector. Dr. Menendez found that oleic acid, the major fatty acid in olive oil, is highly effective in killing the Her2/neu protein, a major factor in the growth of breast cancer tumours. The oil is, as a matter of fact, just as effective as the anticancer drug Herceptin and, when combined with this drug, results in a reduction of 70% in Her2/neu levels (in test tube experiments). Dr. Menendez suggests that olive oil manufacturers should begin to list the total oleic acid content on their products so that consumers can select the best brand for cancer prevention.
New Scientist, January 15, 2005, p. 7

Carrots and fish help prevent breast cancer
MONTREAL, CANADA. Breast cancer is the most common cancer in Canadian women. In 2002, about 20,700 new cases were diagnosed and 5,400 women died from the disease. Many studies, most of them inconclusive, have been carried out to seek correlations between diet and the risk of breast cancer. Researchers at the University of Montreal now report that a diet rich in carotenoids and fish oils may reduce breast cancer risk. Their study involved 411 French-Canadian women diagnosed with breast cancer and 429 matched controls. All participants completed validated food-frequency questionnaires in face-to-face interviews. The interviewers found no overall correlation between carotenoid intake and cancer risk; however, they did find intriguing correlations in subgroups of women.

Among premenopausal women who were now smoking or had smoked in the past, a high intake of alpha- carotene was associated with a 2.4-fold increase in cancer risk. Among postmenopausal women total intake of carotenoids was associated with a 1.92-fold increase in risk if combined with a high intake of arachidonic acid. However, if a high intake of carotenoids was combined with a high intake of docosahexaenoic acid (DHA), a main component of fish oils, the cancer risk was cut in half. These associations remained after adjustments for other known breast cancer risks such as age at first full-term pregnancy, history of breast cancer in first-degree relatives, history of benign breast disease, number of full-term pregnancies, martial status, and calorie intake. The researchers conclude that a diet with a high content of fruits, carotenoid-rich vegetables, and DHA-rich fish may reduce the risk of breast cancer.
Nkondjock, A. and Ghadirian, P. Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal, Canada. American Journal of Clinical Nutrition, Vol. 79, May 2004, pp. 857-64

Editor's comment: Several studies have shown that fish oil supplementation is just as effective as eating whole fatty fish when it comes to realizing the benefits of fish consumption.

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Folic acid and B vitamins help prevent breast cancer
BOSTON, MASSACHUSETTS. Researchers at the Harvard School of Public Health have released the results of a major study aimed at evaluating the association between blood (plasma) levels of folate (folic acid), vitamins B6 and B12 and the risk of breast cancer. The study involved 32,826 female nurses who had blood samples drawn during 1989 and 1990. At the end of 1996 712 of the participants had developed breast cancer.

The researchers found the women with the highest plasma levels of folate (greater than 14 ng/mL) had a 27% lower risk of breast cancer than did women with a lower level (less than 6.4 ng/mL). The protective effect of folic acid was found to be even more pronounced in women who regularly consumed alcohol (one drink per day or more). Here those with the highest folate levels had an 89% lower risk of breast cancer than did women with low levels.

High plasma levels of vitamin-B6 (greater than 95.3 pmol/mL) were associated with a 30% risk reduction as compared to low levels (less than 28.5 pmol/mL). High vitamin B12 levels were associated with a lower breast cancer risk among premenopausal women, but not among postmenopausal women. This finding contradicts that of earlier studies which found a protective effect only among postmenopausal women. It is interesting that no correlation was observed between the intake of vitamin B12 from food and plasma levels; a significant correlation was noticed between vitamin-B12 intake from supplements and plasma levels. Plasma homocysteine levels were not associated with breast cancer risk. The researchers conclude that folic acid and vitamin B6 may help prevent breast cancer and that ensuring an adequate intake of these vitamins either from food or supplements may reduce breast cancer risk.
Zhang, SM, et al. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. Journal of the National Cancer Institute, Vol. 95, March 5, 2003, pp. 373-80

Folic acid prevents breast cancer
SHANGHAI, CHINA. A team of American and Chinese researchers has discovered that folic acid (folate) is highly effective in preventing breast cancer in both pre- and postmenopausal women. Their investigation involved 1321 women with breast cancer and 1382 healthy controls. The women were between the ages of 25 and 64 years when they enrolled in the Shanghai Breast Cancer Study during 1996-98.
The researchers found a clear correlation between dietary intake of folic acid and the risk of breast cancer. Women with a daily intake of 345 micrograms or higher had a 38 per cent lower risk than did women with an intake of less than 195 micrograms - after adjustment for total vegetable, fruit and animal food intake. The protective effect of folic acid was even more pronounced in women who also had a high dietary intake of vitamin B6, vitamin B12 and methionine. Women with a daily intake equal to or higher than 345 micrograms of folic acid, 8.47 micrograms of vitamin B12, 2 mg of vitamin B6, and 1.9 grams of methionine had a 53 per cent lower risk of breast cancer than did women with daily intakes at or below 195 micrograms of folic acid, 1.32 micrograms of vitamin B12, 1.35 mg of vitamin B6, and 1.27 grams of methionine.
Researchers believe that folic acid exerts its protective effect by preventing errors in DNA replication and by helping to regenerate methionine, a vital component in DNA synthesis. They also point out that both vitamin B12 and vitamin B6 are vital cofactors required for folic acid to "do its job". NOTE: Most multivitamins have levels of folic acid, vitamin B6 and vitamin B12 well above the levels found to be beneficial in the Shanghai study.
Shrubsole, Martha J., et al. Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Research, Vol. 61, October 1, 2001, pp. 7136-41

Physical activity and breast cancer risk
CALGARY, CANADA. Canadian researchers have released the results of a major study evaluating the effect of lifetime physical activity on breast cancer risk. The study included 1233 women with breast cancer and 1237 controls and was conducted in Alberta during the period 1995-97. All study participants underwent comprehensive interviews to determine their lifetime physical activity level, diet, smoking status, alcohol consumption, reproductive history, and body measurements. The researchers found no correlation between lifetime physical activity level and breast cancer risk in premenopausal women. Among postmenopausal women, however, they observed a clear risk reduction with increased household and occupational physical activity, but not with increased recreational physical activity. Women who had been most active during their lifetime (household and occupational) had an almost 40 per cent lower risk of breast cancer than did less active women. Active women who did not consume alcohol had a 61 per cent lower risk and active women who had not had any children (nulliparous) had a 78 per cent risk reduction. The researchers conclude that a high level of physical activity over a lifetime reduces the risk of breast cancer in postmenopausal women.
Friedenreich, C.M., et al. Case-control study of lifetime physical activity and breast cancer risk. American Journal of Epidemiology, Vol. 154, August 15, 2001, pp. 336-47

Glucarate and breast cancer prevention
LAWRENCEVILLE, NEW JERSEY. So far the "war on cancer" initiated by President Nixon in 1971 has had a fairly limited success. In 1971 a total of 635,000 new cases of cancer was diagnosed in the USA; by the year 2000 this number had risen to 1,225,000 - an increase of 93 per cent. The number of new cases of breast cancer has increased by about 61 per cent since 1973 and now stands at 184,000 annually. A 1991 report issued by the US Government Accounting Office concluded that there had been no progress in the prevention of breast cancer or in reducing mortality from breast cancer.
Researchers at the Simone Protective Cancer Institute point out that perhaps 90 per cent of all cancers are caused by dietary or nutritional factors. It is also clear that inadequate removal or detoxification of carcinogenic substances in the body plays a significant role in cancer initiation and progression. Evidence is mounting that a simple natural compound, glucarate, found in many vegetables and fruits is very effective in boosting the immune system and detoxifying the body. Calcium glucarate converts to D- glucaric acid in the stomach and is the precursor of the enzyme glucuronyl transferase. This enzyme binds to carcinogens like polycyclic aromatic hydrocarbons, nitrosamines, and steroids and safely excretes them. Animal experiments have found glucarate effective in inhibiting cancers of the colon, skin, lung, and breast and it alone or in combination with vitamin A has been found to inhibit the growth of human breast cancer cells. Glucarate is effective in doses from 1 gram/kg of body weight to 27 grams/kg of body weight.
Simone, Charles B., et al. Cancer, lifestyle modification and glucarate. Journal of Orthomolecular Medicine, Vol. 16, No. 2, 2nd Quarter 2001, pp. 83-90 [86 references]
Webb, T.E., et al. Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate/retinoid combination. Anticancer Research, Vol. 13, No. 6A, November-December 1993, pp. 2095-99

Beta-carotene and breast cancer
NEW YORK, NY. Carotenoids, like beta-carotene, are important constituents of fruits and vegetables. Numerous studies have investigated the association between the dietary intake of carotenoids and the risk of breast cancer. Some have found a beneficial effect, others have not. Researchers at the New York University School of Medicine now weigh in with the results of a new study that shows a clear benefit of carotenoids.
Their study involved 270 women diagnosed with breast cancer and 270 matched controls (125 pre- and 145 postmenopausal in each group). All the participants had blood samples taken at the beginning of the study in 1985 (at least 6 months and more likely an average of four years prior to the cancer diagnosis). These samples were frozen at minus 80 degrees Celsius until analysis in 1995. The researchers found that women with the lowest levels of carotenoids in their blood serum had twice the incidence of breast cancer than did women with the highest levels (highest quartile). The specific odds ratios were 2.21 for beta-carotene, 2.08 for lutein, 1.68 for beta-cryptoxanthin, and 2.0 for alpha-carotene. The researchers conclude that, "These observations offer evidence that a low intake of carotenoids, through poor diet and/or lack of vitamin supplementation, may be associated with an increased risk of breast cancer".
Toniolo, Paolo, et al. Serum carotenoids and breast cancer. American Journal of Epidemiology, Vol. 153, June 15, 2001, pp. 1142-51

Fish oils may help prevent breast cancer
LOS ANGELES, CALIFORNIA. Animal experiments have shown that a diet rich in linoleic acid (omega-6 fatty acids) promotes the growth of malignant breast cancer tumors. Addition of omega-3 polyunsaturated fatty acids to the diet can block this effect. Epidemiological studies have shown that countries with a high intake of omega-3 acids from fish have lower breast cancer rates. These findings prompted medical researchers at the University of California School of Medicine to speculate that the ratio of omega-3 to omega-6 fatty acids in the diet may explain international differences in cancer rates. As a first step in proving this hypothesis the researchers decided to find out if adding omega-3 fatty acids to the diet would actually increase the omega-3 content and the omega-3 to omega-6 ratio in the breast tissue of women with breast cancer.

Their study involved 25 women who had been diagnosed with high-risk (stage II or III) localized breast cancer. A low fat diet containing 15% of calories from fat, 15% from protein, and 70% from carbohydrates was designed for the women. In addition, they were given 10 fish oil capsules a day providing a total of 3 grams of omega-3 polyunsaturated fatty acids (18% eicosapentaenoic acid [EPA] and 12% docosahexaenoic acid [DHA]). After 3 months on this regimen the study participants provided fasting blood samples and biopsy specimens from the breast and buttock adipose tissue. The researchers found a marked increase in the levels of EPA and DHA in blood plasma, breast tissue, and gluteal tissue. A reduction in omega-6 fatty acid level was observed in blood plasma, but not in the breast or gluteal tissues. The omega-3 to omega-6 ratio in the blood increased by a factor of 4 (from 0.09 to 0.41) and rose from 0.05 to 0.07 in the breast tissue. The researchers conclude that fish oil supplementation is an effective way of altering the fatty acid availability in tumor tissue and thereby possibly affect tumor growth. They plan to further study the relationship between omega-3 to omega-6 ratio and breast cancer risk.
Bagga, Dilprit, et al. Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer. Journal of the National Cancer Institute, Vol. 89, August 6, 1997, pp. 1123-31

Omega-3 fatty acids and breast cancer
ROCHESTER, NEW YORK. Dr. William Cave, MD of the University of Rochester School of Medicine presents an overview of the current knowledge regarding the relationship between dietary intake of essential fatty acids and breast cancer. Dr. Cave reviews the experimental evidence (mostly based on animal tests) supporting the contention that omega-6 polyunsaturated fatty acids promote tumor formation while omega-3 acids retard tumor development. A particularly interesting observation is the finding that rats fed a diet containing 20% coconut oil, butter or tallow had half the number of breast tumors than did rats fed a diet containing equivalent amounts of cottonseed oil, sunflower seed oil or corn oil (all high in omega-6 content). However, when as little as 3% of the coconut oil was replaced by sunflower seed oil the number of tumors increased to equal that obtained with 20% sunflower seed oil alone. This indicates that there is a certain, fairly low, level of omega-6 fatty acids which will lead to increased tumor formation irrespective of the composition of the rest of the diet. Animal experiments have also shown that fish oils are highly effective in preventing the development and progression of breast tumors and can diminish the metastatic spread of breast cancer. Dr. Cave concludes that changes in dietary fat composition can significantly affect breast cancer development and suggests the differences in eisosanoid metabolism induced by the two essential fatty acid families (omega-3 and omega-6) may be an important factor.
Cave, William T., Jr. Dietary omega-3 polyunsaturated fats and breast cancer. Nutrition (Supplement), Vol. 12, No. 1, 1996, pp. S39-S42

Fat consumption and cancer
LONDON, UNITED KINGDOM. Several major epidemiologic studies have found a clear association between a high dietary fat intake and the risk of developing breast and colon cancer. The correlation is particularly strong in the case of animal fats. One study found that a high fish or fish oil consumption is protective against later stage colon cancer in men, but has no effect on mortality from breast cancer. British medical researchers now report that fish and fish oils not only protect against colon cancer in men, but also against colon and breast cancer in women. This protective effect, however, is only apparent in countries where the intake of animal fats is high. In other words, a high intake of fish or fish oils counteracts the detrimental effects of a high animal fat consumption.

The study compared cancer mortality rates in 24 European countries, Canada and the USA with fish consumption and the intake of animal fats. In countries where the animal fat intake was high the researchers found a clear inverse correlation between the ratio of fish fat to animal fat and the risk of developing breast cancer in women and colon cancer in both men and women. A similar correlation was found between cancer risk and the ratio of fish fat to total fat intake.

The researchers conclude that a 15% decrease in animal fat intake combined with a 3-fold increase in fish oil intake could possibly reduce male colon cancer risk by as much as 30% in countries with a high animal fat intake. A 3-fold increase in fish oil intake could be achieved by eating fish three times a week or by taking two standard fish oil capsules daily.
Caygill, C.P.J., et al. Fat, fish, fish oil and cancer. British Journal of Cancer, Vol. 74, No. 1, July 1996, pp. 159-64

Safety of tamoxifen trial questioned
WASHINGTON, DC. A new breast cancer prevention trial is underway in the United States and Canada. The study involves 16,000 healthy women and is designed to find out whether tamoxifen is effective in preventing breast cancer, heart attack, and bone fractures. Now two doctors, Adriane Fugh-Berman of the National Women's Health Network and Samuel Epstein of the University of Illinois caution women against participating in the trial. They point out that the supposed benefits of tamoxifen are based on tenuous evidence and that the drug has many known toxic effects. Among these are increased risk of endometrial and liver cancer, hepatitis, retinopathy, and stroke. The doctors point out that the consent form for participating in the trial minimizes the risks and exaggerates the potential benefits.
The New England Journal of Medicine, November 26, 1992, p. 1596

Yogurt fights cancer - maybe?
BOSTON, MASSACHUSETTS. A low fat, high fiber diet is highly effective in preventing both breast and colon cancer. Recent research has shown that the risk of developing breast cancer is related to the amount of estrogen circulating in the blood stream; the more estrogen, the higher the risk. Now evidence is mounting that estrogen levels are directly related to the fat and fiber content of the diet. A group of healthy American women switched from a high-fat, low-fiber diet (40% of calories as fat and 12 g/day of fiber) to a low-fat, high-fiber diet (20% of calories from fat and 40 g/day of fiber). Within two months their estrogen level had dropped by 46%. The risk of colon cancer is also directly related to total intake of animal fat, but not to vegetable fat intake. A group of American nurses who regularly ate red meat was found to have an increased risk of colon cancer while those who ate fish and chicken had a lower risk. Other studies have shown that eating a high-fiber diet can reduce colon cancer risk by as much as 50% over eating a low-fiber diet. Now researchers at the Tufts University School of Medicine have found that probiotics (lactobacillus and bifidobacterium) exerts a protective effect in the colon. Experiments have shown that consuming lactobacillus acidophilus either as such or in the form of yogurt significantly reduces the amount of cancer-initiating enzymes in the colon. The researchers point out that commercial yogurt produced using lactobacillus bulgaricus and streptococcus termophilus are ineffective in colon cancer prevention.
Gorbach, Sherwood L. and Barry R. Goldin. Nutrition and the gastrointestinal microflora. Nutrition Reviews, Vol. 50, No. 12, December 1992, pp. 378-81

Breast cancer rates related to fat intake
LEUVEN, BELGIUM. Researchers at the University of Leuven have completed a study to determine the relationship between fat intake and breast cancer rates in 30 countries. They used nutritional surveys as well as dietary data supplied by the United Nations. They found that breast cancer rates were highly correlated with the intake of animal fats. Intake of fat from fish on the other hand, appeared to have a protective effect. The detrimental effects were greatest in women over 50. The researchers also found a lag time of about 10 years between breast cancer rates and changes in fat intake or compostion.
Sasaki, Satoshi, et al. An ecological study of the relationship between dietary fat intake and breast cancer mortality. Preventive Medicine, March 1993, pp. 187-202

Don't stay out of the sun
MEADOW VISTA, CALIFORNIA. Sunlight in moderation is good for you and may actually prevent cancer rather than cause it. Mounting scientific evidence shows that regular exposure to sunlight lowers the risk of developing breast cancer. As a matter of fact, excessive sun avoidance and use of sunscreens have now been linked with an increase in cancer. A researcher in California estimates that a widespread public adoption of regular sunbathing would result in 32,000 fewer deaths from colon and breast cancer every year in the U.S.A. alone. Dr. Ainsleigh also points out that it is severe sunburning which initiates melanoma while regular long-term sun exposure actually inhibits it. There is now also evidence that regular sunscreen use is associated with a higher incidence of melanoma. It is thought that the cancer- protecting effect of sunlight is related to its ability to produce vitamin D in the body. This synthesis continues for several days after exposure. Dr. Ainsleigh recommends daily sunbathing for short periods of time with as much skin exposed as possible except for the head and neck area which should be protected with a hat.
Ainsleigh, H. Gordon. Beneficial effects of sun exposure on cancer mortality. Preventive Medicine, January 1993, pp. 132-140

Cancer prevention: sleep in the dark?
SEATTLE, WASHINGTON. Researchers at the Fred Hutchinson Cancer Research Center in Seattle have embarked upon a $3 million study to determine if avoidance of light and other electromagnetic radiation at night can prevent breast cancer. Dr. Scott Davis speculates that the reason why exposure to electromagnetic fields results in an increased risk for cancer is that the fields interfere with the production of the hormone melatonin. Melatonin is formed in the pineal gland and its production reaches its peak around 2 a.m. when no light reaches the retina. Studies have shown that melatonin is a potent killer of breast cancer cells. The 4-year study will match 800 women with breast cancer with 800 healthy women. The exposure to light and other radiation for the past decade will be estimated for all the women and direct measurements of light and electric field exposure will also be made. Particular emphasis is being placed on determining the effect of exposure to light at night. The study will attempt to determine exposure to street lights and lighted signs from nearby stores as well as to other exterior or interior light sources.
Waalen, J. Nighttime light studied as possible breast cancer risk. Journal of the National Cancer Institute, Vol. 85, No. 21, November 3, 1993, pp. 1712-13

Womens' health study largest yet
BETHESDA, MARYLAND. The National Institutes of Health in the U.S.A. is embarking upon its largest study yet of disease prevention in women. The 15-year study involves more than 160,000 women aged 50 to 79 years and is aimed at determining the major causes of disability, frailty, and death in older women. Part of the study is a large clinical trial involving 63,000 women which will run for nine years. This trial will hopefully provide definitive answers to the following questions:

  • Does a low fat diet prevent heart disease, breast cancer and colorectal cancer ?
  • Does hormone replacement therapy (estrogen or estrogen plus progestin) prevent cardiovascular heart disease and osteoporosis ?
  • Does supplementation with calcium and vitamin D prevent colorectal cancer and osteoporotic fractures ?
The organizers of the study also hope to shed light on such questions as whether women have different risk factors than men for common chronic diseases, whether weight change predicts illness and whether low cholesterol levels are a cause or a result of chronic diseases which are not cardiovascular in origin.
Kirschstein, Ruth. Largest US clinical trial ever gets under way. Journal of the American Medical Association, Vol. 270, No. 13, October 6, 1993, p. 1521

Vitamin A may protect against breast cancer
BOSTON, MASSACHUSETTS. Evidence is mounting that a high intake of fruits and vegetables is protective against most cancers. It is not entirely clear which components of the fruits and vegetables provide the protection but vitamin C and beta carotene have long been top contenders. Now researchers at the Harvard Medical School report that folic acid may provide significant protection against colon cancer. The scientists found that men and women with a high intake of folic acid (including supplements) had a 35 per cent less risk of developing adenomatous colon polyps (the precursors to colon cancer) than did people with a low intake. A high fiber intake was also found to lower the colon adenoma risk. Thus people who consumed about 30 grams/day of fiber had a 50 per cent lower risk than did people who consumed about 12 grams/day. The researchers also report on the latest findings in the Nurses' Health Study concerning breast cancer. Between 1980 and 1988 about 1500 cases of breast cancer occurred in the study group. The scientists found no correlation between the risk of breast cancer and the intake of fat or the intake of vitamins C and E. However, a high intake of vitamin A was found to correspond to a 20 to 30 per cent reduction in breast cancer risk. The researchers believe that both beta carotene and preformed vitamin A from animal sources (including supplements) have a protective effect. They point out that women who already have a high dietary intake of vitamin A may benefit little from further supplementation; however, among women whose dietary intake was low, the scientists found a 50 per cent reduction in breast cancer risk associated with the use of vitamin A supplements.
Willett, Walter C. Micronutrients and cancer risk. American Journal of Clinical Nutrition, Vol. 59 (suppl), May 1994, pp. 1162S-65S

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Alpha-linolenic acid prevents breast cancer from spreading
TOURS, FRANCE. Medical doctors at the University Hospital in Tours have discovered that breast cancer victims who have a high content of alpha-linolenic acid (9,12,15-octadecatrienoic acid) in their breast tissue are less likely to develop metastases (cancer in distant organs such as the stomach, intestines, etc.). The study involved 121 women who had been diagnosed with localised breast cancer. The researchers analyzed samples of adipose (fatty) tissue taken close to the tumor at the time of surgery. They found that the cancer was more likely to have spread to the lymph nodes in the armpits in women with a low level of alpha-linolenic acid in their tissue. They found no relationship between alpha- linolenic acid content and tumor size. After an average follow up of 31 months, 21 of the women developed metastases. The researchers discovered that women who had a high adipose tissue content of alpha-linolenic acid at the time of surgery were five times less likely to have developed metastases than did women with a low content (<0.38 per cent). Original tumor size was also an important factor in predicting risk of metastasis which is the main cause of death among breast cancer patients. Women who had a tumor with a diameter greater than 5 cm had a 4.7 times greater risk of developing metastases than did women with smaller tumors. The researchers conclude that dietary supplementation with alpha- linolenic acid might delay or prevent the development of metastases in breast cancer patients. They also point out that previous research has shown that a high intake of dietary fat originating from fish helps prevent breast cancer in the first place and also improves survival among breast cancer patients. NOTE: Flax oil, pumpkin oil and purslane are good sources of alpha-linolenic acid.
Bougnoux, P., et al. Alpha-linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. British Journal of Cancer, Vol. 70, No. 2, August 1994, pp. 330- 34

Diet is important for breast cancer survival
TORONTO, CANADA. Researchers at the National Cancer Institute of Canada have found that diet and vitamin intake are important factors in determining survival from breast cancer. Their study involved 678 women who were diagnosed with breast cancer between January 1982 and June 1992. Seventy-six of the women died from the cancer during the review period. After studying the dietary habits of the women prior to their cancer diagnosis, the researchers concluded that the risk of dying from breast cancer increases by 50 per cent for every 5 per cent (per cent of energy) increase in the intake of saturated fat. They also found that women who had a relatively high intake of beta-carotene (>7690 IU/day) had half the risk of dying from breast cancer than did women with a low intake (<3607 IU/day). Vitamin C was also found to be protective. Women consuming more than 210 mg/day had a 57 per cent lower risk of dying from breast cancer than women getting less than 110 mg/day. Vitamin E also showed a slight protective effect despite the fact that the amounts consumed by the women were very small, ie. 24 IU per day or less.
Jain, Meera, et al. Premorbid diet and the prognosis of women with breast cancer. Journal of the National Cancer Institute, Vol. 86, No. 18, September 21, 1994, pp. 1390-97

Exercise protects against breast cancer
LOS ANGELES, CALIFORNIA. It is generally accepted that regular exercise has a protective effect against many chronic diseases such as heart disease, stroke, diabetes, osteoporosis, colon cancer, and endometrial cancer. Now researchers at the University of Southern California provide convincing proof that exercise also protects against breast cancer. The researchers studied 545 women who had been diagnosed with in situ or invasive breast cancer between July 1, 1983 and January 1, 1989. The women were matched with 545 cancer-free controls. All the women were white and less than 40 years old at the time of their breast cancer diagnosis. The researchers found that women who had participated in regular physical exercise for at least four hours per week since their first menstrual period had a 50 per cent lower risk of developing breast cancer than did inactive women. Women who spent one to three hours per week in physical activity had a 30 per cent lower risk. The physical activities considered as exercise in the study included participation on a sports team, dance or exercise classes, swimming, gymnastics, workouts at gyms, running/jogging, and walking for exercise. The researchers believe that exercise protects against breast cancer by reducing the frequency of menstrual cycles or by reducing the length of the luteal phase (latter part of menstrual cycle). This in turn leads to a reduction in the cumulative exposure to progesterone and estrogen (estradiol). There is now strong evidence that breast cancer risk is directly related to the cumulative exposure to ovarian hormones.
Bernstein, Leslie, et al. Physical exercise and reduced risk of breast cancer in young women. Journal of the National Cancer Institute, Vol. 86, No. 18, September 21, 1994, pp. 1403-08

Fruits and vegetables protect against breast cancer
ATHENS, GREECE. Researchers at the Athens Medical School and the Harvard School of Public Health have just completed a major study aimed at determining the effect of diet on the risk of developing breast cancer. Their investigation involved 820 women with breast cancer and 1548 controls. The researchers found that women who ate large quantities of fruits had a 35 per cent lower risk of developing breast cancer than did women who consumed only small amounts. The risk factor among women who ate lots of vegetables was 46 per cent lower than among women who only ate few vegetables. A high consumption of olive oil also conferred significant protection. Women who consumed olive oil more than once per day were 25 per cent less likely to develop breast cancer than were women who used olive oil once per day or less. The protective effect of olive oil was particularly strong among postmenopausal women whereas the beneficial effect of fruits and vegetables was found in all age groups. A high margarine consumption was found to significantly increase the risk of developing breast cancer. There was no indication that the consumption of butter is related to the risk of breast cancer.
Trichopoulou, Antonia, et al. Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. Journal of the National Cancer Institute, Vol. 87, No. 2, January 18, 1995, pp. 110-16

Vitamin C, carotene, and fiber protect against breast cancer
SHANGHAI, CHINA. Chinese and American researchers report the results of a large study designed to evaluate the relationship between diet and breast cancer. The study involved over 800 Chinese women (aged 20 to 69 years) with confirmed breast cancer and a similar number of matched controls. The researchers found that women with a high fat intake (mainly from pork) and a low crude fiber intake had a 2.4 to 2.9 times greater risk of developing breast cancer than did women with a low fat intake and a high fiber intake. The researchers conclude that a diet high in fiber, vitamin C, and carotene has a strong protective effect against the development of breast cancer. They also conclude that a high fat intake may promote breast cancer in a minor way. They did not find any evidence that a high intake of soy protein has a protective effect. Note: The overall breast cancer rate in the study area is about 19 per 100,000 women or 20 per cent of the comparable rate among white women in the United States.
Yuan, J.M., et al. Diet and breast cancer in Shanghai and Tianjin, China. British Journal of Cancer, Vol. 71, June 1995, pp. 1353-58

Free radicals implicated in spread of breast cancer
SEATTLE, WASHINGTON. There is substantial evidence that free radical attacks on DNA are a major factor in the initiation of cancer. Now researchers at the Pacific Northwest Research Foundation and the University of Seattle report that free radicals, specifically hydroxyl radicals, are intimately involved in the spread (metastasis) of breast cancer. The researchers studied breast tissues from 12 women with invasive ductal carcinoma but no lymph node involvement, 25 women with metastasized invasive ductal carcinoma, and 21 women with no evidence of breast cancer. Using highly sensitive analysis techniques (FT-IR spectroscopy and GC-MS) the researchers determined that women with metastasized breast cancer exhibit twice as much free-radical damage to the breast tissue DNA than do women with localized cancer. They also found a clear correlation between the growth of metastatic tumours and the extent of radical-induced DNA damage. The researchers conclude that antioxidants, especially vitamin C, may play a crucial role in controlling free radical damage to the DNA in breast tissue and may help prevent metastasis.
Malins, Donald C., et al. Progression of human breast cancers to the metastatic state is linked to hydroxyl radical-induced DNA damage. Proceedings of the National Academy of Sciences USA, Vol. 93, No. 6, March 19, 1996, pp. 2557-63

Exercise helps prevent breast cancer
TROMSO, NORWAY. Researchers at the University of Tromso report that women who exercise regularly reduce their risk of developing breast cancer substantially. Their study involved over 25,000 women aged 20 to 54 years at the entry to the study. During the 14-year follow-up period 351 of the women developed invasive breast cancer. The researchers found that younger, premenopausal women (less than 45 years of age) who exercised regularly had a 62 per cent reduction in risk as compared to sedentary women. The risk reduction was even higher for lean women (body mass index <22.8) who exercised more than four hours per week; these women had a 72 per cent reduction in risk. The reduction in breast cancer risk among postmenopausal women who exercised was less than than for younger women, but still highly significant. Both regular exercise and extensive physical activity during work were found to have a protective effect. The researchers speculate that regular physical activity lowers a woman's cumulative exposure to estrogen and progesterone, thereby inhibiting the development of breast cancer. Physical activity may also exhibit its protective effect by reducing obesity. Interestingly enough, the researchers also discovered that taller women were at increased risk while having a greater number of children reduced the risk. They found no correlation between total fat intake and breast cancer risk.
Thune, Inger, et al. Physical activity and the risk of breast cancer. New England Journal of Medicine, Vol. 336, May 1, 1997, pp. 1269-75

Iodine combats breast cysts
We do not as a rule report on items from newspapers; this one, however, is so intriguing that we thought we would make an exception. Please bear in mind that iodine supplementation may not be advisable for everyone particularly for those with thyroid problems. Please check with your physician before embarking on self-medication.

VICTORIA, CANADA. Dr. David Derry received his MD from the University of British Columbia, a PhD in biochemistry from McGill University, and was assistant professor in pharmacology at the University of Toronto - impeccable credentials indeed. He has been practising as a family doctor in Victoria for the last 25 years. In 1993 Dr. Derry became intrigued by a report in the Canadian Journal of Surgery which described the benefits of iodine in reducing fibrocystic breast lumps. Since then he has advised over 200 of his female patients to take extra iodine in order to remove cysts. The results have been spectacular. Although complete disappearance of the lumps may take anywhere from two months to two years the success rate so far has been 100 per cent. Dr. Derry is adamant that most women do not get nearly enough iodine in their diet to protect their breasts against lump formation and also believes that a lack of iodine may be an important risk factor for breast cancer. He recommends 5-10 drops (milligrams) per day of a preparation of calcium, potassium, and iodide (Lugol's solution) taken in a glass of orange juice. However, some of his patients have found just one drop a day to be beneficial. NOTE: Antiseptic iodine is not recommended as it contains poisonous wood alcohol.
Dedyna, Katherine. Iodine: Bosom buddy. Times Colonist, September 9, 1997, p. D1

Phyto-estrogens prevent breast cancer
PERTH, AUSTRALIA. Phyto-estrogens are naturally occurring components of many plants which have a structure similar to that of estrogen. The two main varieties of phyto-estrogens are isoflavonoids such as daidzein, genistein and equol, and lignans such as enterodiol, enterolactone and matairesinol. Now Australian researchers report that women with a high intake of equol (found in soy foods and cow's milk) have a four-fold lower risk of developing breast cancer than do women with a low intake. Women with a high intake of the lignan enterolactone (found in whole grains, berries, flax seed, and fruits and vegetables) had a three-fold reduction in risk. This risk reduction remained valid after adjustment for other known or suspected risk factors for breast cancer such as age of first menstruation, pregnancies, alcohol consumption, and dietary fat intake. The study involved 144 women aged 30 to 84 years who had just been diagnosed with early breast cancer and 144 matched controls. All the breast cancer patients provided 72-hour urine collection and blood samples before any treatment was started. The urine samples were analyzed for phyto-estrogen content using isotope-dilution gas chromatography-mass spectrometry and the results compared to the results obtained on similar samples from the controls. The researchers found that the breast cancer patients had much lower concentrations of equol and enterolactone in their urine than did the controls and conclude that a high intake of phyto-estrogens is protective against breast cancer. Note: The researchers had problems with the analysis of genistein and could not reach a valid conclusion regarding its effects.
Ingram, David, et al. Case-control study of phyto-oestrogens and breast cancer. The Lancet, Vol. 350, October 4, 1997, pp. 990-94
Messina, Mark, et al. Phyto-oestrogens and breast cancer. The Lancet, Vol. 350, October 4, 1997, pp. 971-72 (commentary)

Tamoxifen in breast cancer prevention
MILAN, ITALY. Tamoxifen has proven effective in reducing the risk of new tumors developing in breast cancer patients. The drug slows the growth of the tumors and shrinks them by cutting off the estrogen supply. Tamoxifen only works for about five years after which cancer cells adapt to it and may actually feed on it. It's effects in breast cancer patients has spawned the idea that it may also work as a preventive measure. A large American trial, the Breast Cancer Prevention Trial, involving over 13,000 women recently concluded that taking tamoxifen for preventive purposes led to a 45 per cent reduction in breast cancer risk. Now Italian and British researchers question this conclusion. A trial involving almost 4,000 women, mostly of Italian origin, is being conducted by the European Institute of Oncology. The women (aged 35 to 70 years) who had all undergone a hysterectomy were randomized into two groups, one receiving 20 mg tamoxifen daily, the other receiving a placebo. After a median follow-up of 46 months 41 cases of breast cancer had occurred with no statistically significant difference in occurrence between the two groups. However, tamoxifen did seem to confer some protection among women who also used hormone replacement therapy (HRT). Eight cases of breast cancer occurred among the 390 women allocated to the placebo group compared to one case among the 362 women taking tamoxifen. Among the 1576 women in the placebo group not using HRT 13 developed breast cancer as compared to 17 cases in the tamoxifen group (1509 women not using HRT). There were 14 documented cerebrovascular events, five in the placebo group and nine in the tamoxifen group. All five confirmed strokes were in the tamoxifen group. Hypertriglyceridemia was also significantly more prevalent in the tamoxifen group. The Italian researchers conclude "tamoxifen was not significantly protective against breast cancer in women at normal or slightly reduced risk of the disease, at least in the duration of our follow-up".

British researchers reporting on the Royal Marsden Hospital tamoxifen trial reached a similar conclusion in a trial involving 2494 women aged 30 to 70 years with a family history of breast cancer. They were unable to show any protective effect of tamoxifen in healthy women after an eight-year follow-up. They did find that women who started HRT during the trial had a reduced risk of breast cancer while women who were already on HRT at the start of the trial had an increased risk. The British researchers conclude that there is currently no justification for advising high-risk women to take tamoxifen to prevent breast cancer.

Dr. Kathleen Pritchard of the University of Toronto reviews the British and Italian trials in an editorial and suggests that they "cast doubt on the wisdom of the rush, at least in some places, to prescribe tamoxifen widely for prevention".
Veronesi, U., et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. The Lancet, Vol. 352, July 11, 1998, pp. 93-97
Powles, Trevor, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. The Lancet, Vol. 352, July 11, 1998, pp. 98-101
Pritchard, Kathleen I. Is tamoxifen effective in prevention of breast cancer? The Lancet, Vol. 352, July 11, 1998, pp. 80-81 (commentary)

Antioxidants help prevent breast cancer
JEFFERSON, ARKANSAS. Oxidative stress damages DNA, proteins, cell membranes and mitochondria, and is believed to play a role in breast cancer. The body produces certain enzymes (glutathione, catalase, and superoxide dismutase) which along with antioxidants obtained from the diet (vitamins E and C, selenium, and carotenoids) help protect against oxidative stress. Manganese superoxide dismutase (MnSOD) has the specific task of protecting the mitochondria (the cells' "powerplant") from oxidative damage. MnSOD is a complex protein and comes in two genetically different forms (alleles). Researchers at the National Center for Toxicological Research have just published a fascinating study which shows that the two MnSOD alleles are not equally effective in protecting the mitochondria and that women who are genetically predisposed to produce the less effective form are at greater risk of developing breast cancer. The study involved 266 women with breast cancer and 295 matched controls. The researchers found that premenopausal women who had the less effective MnSOD version were four times more likely to develop breast cancer than were women with the more effective version. Among postmenopausal women the ratio was 2:1. It was also clear from the study that premenopausal women who had the less effective MnSOD allele, but consumed a diet rich in antioxidants (from fruit and vegetables) were at no higher risk than were women with the more effective MnSOD version. Vitamin C and E supplements were found to be particularly effective in counteracting the "poor" MnSOD form. Premenopausal women who did not supplement with vitamin C had a 4.8 higher risk of developing breast cancer than did women who did supplement. Women who did not take vitamin E were found to have a 3.8 times higher risk than did women who supplemented with vitamin E. The researchers conclude that a high intake of antioxidants (from supplements or fruits and vegetables) will help prevent breast cancer.
Ambrosone, Christine B., et al. Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer. Cancer Research, Vol. 59, February 1, 1999, pp. 602- 06

Folates and cancer prevention
TORONTO, CANADA. Folates (derivatives of folic acid) play a key role in the synthesis, repair, and methylation of DNA. It is therefore not surprising that a deficiency in this essential B vitamin has been implicated in Alzheimer's disease, atherosclerosis, heart attack, stroke, osteoporosis, depression, dementia, cleft lip and palate, hearing loss, Raynaud's phenomenon, and of course, neural tube defects.
There is now also evidence that a folate deficiency may be involved in the development of certain cancers. Dr. Young-In Kim, MD of the University of Toronto presents an overview of the current knowledge regarding the role of folates in cancer prevention. Some 20 studies have been published regarding the association between colorectal cancer (cancer of the colon or rectum) and folate status. Collectively, these studies suggest that people with a high intake of folates can reduce their risk of developing colorectal cancer by about 40 per cent when compared to people with low intakes. A study involving almost 90,000 American female nurses concluded that nurses who had been supplementing with 400 micrograms/day or more of folic acid for 15 years or more had a 75 per cent reduction in the risk of colorectal cancer when compared to people who did not supplement. The evidence concerning folates and breast cancer is not quite as clear. Studies have shown that even moderate alcohol consumption increases the risk of breast cancer and that this risk can be counteracted by supplementing with folic acid. The jury is still out on whether folate supplementation reduces the risk among non-drinkers although one study did show that postmenopausal women could decrease their risk of developing breast cancer by supplementing with folic acid. Another study involving 300 premenopausal women found a 50 per cent lower risk among women whose intake exceeded 304 micrograms/day. Other studies, however, have failed to confirm this effect.
A major study involving over 29,000 male, Finnish smokers found that those who developed pancreatic cancer had a significantly lower blood serum level of folate than did those who did not. A baseline serum folate level above 4.45 ng/mL was associated with a 55 per cent risk reduction when compared to levels below 3.33 ng/mL. An Australian study found a 64 per cent difference in risk between men with the highest folate intake and those with the lowest intake.
Dr. Kim concludes that a moderate increase in folate intake can materially help reduce the risk of certain cancers, but cautions that people who already have cancer should not increase their folate intake as there is evidence that high folate levels may accelerate the growth of existing tumours.
Kim, Young-In. Folate and cancer prevention: a new medical application of folate beyond hyperhomocysteinemia and neural tube defects. Nutrition Reviews, Vol. 57, October 1999, pp. 314- 21

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