IMC PRACTITIONER ARTICLES

Breast Cancer Prevention. Reducing Risk Through Nutrition, Lifestyle & Environmental Action

The Breast Cancer Epidemic

One woman in eight will develop breast cancer in her lifetime, making it – in developed countries (except for Japan) – the most common cause of cancer death. Breast cancer accounts for 500,000 deaths annually. i[i] Ominously, its incidence has risen about 50% since 1950, however rates have leveled during the last decade.ii[ii] Breast cancer survival rates have not improved either, despite chemotherapy.

It is fascinating and important that breast cancer rates vary by where you live. American women woman have about 6 times the risk of Japanese women!iii[iii] Japanese-Americans, however, have the same rate of breast cancer as other Americans. When women migrate to another country their breast cancer rates assume the pattern of their new country within 2 to 3 generations.iv[iv] This points to life style as a crucial factor in breast cancer causation and prevention strategies.Wide variation of breast cancer rates within the U.S. point also to environmental factors.v[v] vi[vi]

Prevention Perspectives

Some people feel that most disease, including breast cancer, is genetically determined. While it is true that having a family history of breast cancer is a risk factor, “breast cancer genes” cause less than 10% of cases. Nutrition and lifestyle are also transmitted through families, but of course these things can be changed, while genes – for the foreseeable future – cannot.

Breast cancer risk is increased by: hormones, diet, alcohol, and smoking, and is prevented by: vitamin A, carotenoids (the pigment in carrots and other vegetables) and exercise.vii[vii] Breast cancer risk is also increased by exposure to industrial hydrocarbons. All of these factors, and others, will be discussed in this essay.

I strongly reject the pessimism about primary prevention expressed by the American Cancer Society (ACS) when they state (wrongly) that there are no practical ways to prevent breast cancer … Since Women may not be able to alter their personal risk factors, the best opportunity for reducing mortality is through early detection” (by mammography.) viii[viii] While mammography is of some value, I believe the ACS underrates the ability of women to change their personal risk factors.

Mammography

Again, while mammography is of value, it is a serious mistake to over-estimate its effectiveness. Surveys have demonstrated that women both greatly overestimate their risk of dying of breast cancer and the effectiveness of screeningix[ix] It is likely that nutrition, lifestyle and environmental action are more effective at reducing breast cancer risk than complying with ACS guidelines for mammographic screening. Nonetheless, studies have shown a 24% reduction in breast cancer mortality among those receiving mammographic screening compared to those who did not.

Breaking this down by age groups – 29% reduction among women between 50 and 69 years of age, a 13% reduction among women 40 to 49 years of age (not statistically significant), and only marginal effects for women between 70 and 74 years of age.x[x] Despite the fears of some women about mammograms, there was no evidence that getting a mammogram causes breast cancer.

Another way of viewing the numbers is to look at the number needed to routinely screen to save one life.xi[xi] For woman between ages 40-49, 2500 must be screened to save one. For woman between ages 50-69, 270 would have to be screened to save one life. Obviously mammograms work much better for woman between 50 and 70. On the other hand, these numbers are not nearly good enough! Fortunately, primary prevention through nutrition, lifestyle and environmental action offer much more hope. For starters, we should be able to reduce our risk to as low as Japan, where the rate is 1/6 of ours!

Environmentalist Perspective

According to Samuel Epstein xii[xii] – the primary proponent of environmental causation of breast cancer – In fact we know a great deal about its avoidable causes, which include:

• Prolonged use of oral contraceptives and Estrogen Replacement Therapy

• High-fat animal and dairy product diets that are heavily contaminated with chlorinated pesticides that are estrogenic and carcinogenic to the breast, and meat contaminated with potent sex hormones following their use to fatten cattle in feed lots prior to slaughter

• Exposure to petrochemical carcinogens in the workplace that put about 1 million U.S. Women at increased risk.

• Exposure to carcinogenic chemicals from hazardous waste sites and petrochemical plants that pollute soil, air and water.

• Exposure to indoor air pollutants, including carcinogenic pesticides and solvents

• Prolonged use of black and dark brown hair dyes

• Heavy smoking and drinking commencing in adolescence

• Inactivity and Obesity

It should be noted, that some of these factors confer relatively small risk, such as – medical estrogens (see below), and that some of these environmental factors can be avoided, such as – high- fat, non-organically produced animal products or hair dyes. Also, it should be noted that while Japanese women are exposed to as much industrial toxins as Americans their breast cancer risk is apparently moderated by their lifestyle, primarily their diet. This fact should not diminish our commitment to environmental clean up, but clearly empowers individuals to protect themselves.

Life Style

Substantial evidence implicates affluent lifestyle as a potent cause of breast cancer.xiii[xiii] xiv[xiv] xv[xv] Data from 66 countries showed that breast cancer mortality was most strongly associated with dietary factors that were typically associated with affluence (or that poverty protects against breast cancer!):

1. Extremely low fat intake early on in life (particularly animal products) may reduce risk.
2. Olive oil-enriched diets may be protective.
3. Increasing vegetable intake and limiting alcohol consumption may have a modest effect on breast cancer risk.xvi[xvi]
4. Fish and cereal products exert protective effects.
5. While obviously not recommended as a cancer protection strategy having more babies is
protective
6. Breast-feeding reduces breast cancer risk

 

Specific Breast Cancer promoters & prevention strategies

Estrogens

Human Estrogen is an important cause of breast cancer. 16-α hydroxyestrone – a metabolite of estrogen activates estrogen receptors that may trigger breast cancer by strongly increasing the interaction between estrogen receptors and growth-promoting genes, enhancing breast-cell proliferation and perhaps damaging DNA.

A variety of factors impact the levels of “bad” estrogen metabolites. Reducing fat in the diet below 20% of calories lowers estrogen levels, which in turn reduces 16-αhydroxyestrone. xvii[xvii]Phytoestrogens found in foods such as Soy, Apples, Rhubarb, Carrots, Pomegranate seeds, Dates, Onions, Radishes, Cucumbers, Peas, Cabbage, Legumes & Hops yield 2-hydroxyestrone which blocks 16-α hydroxyestrone. Asian females who have a reduced incidence of breast cancer have higher levels of 2-hydroxyestrone and lower levels of 16-α hydroxyestrone than non-Asian women and they eat more soy products and green vegetables.xviii[xviii] A case control study in European women similarly demonstrates the protective effects of dietary phytoestrogens.xix[xix] Cruciferous Vegetables – (Broccoli, Brussels’ Sprouts, Cabbage, Cauliflower) have isothiocyanates such as indole-3-carbinol that also increase the 2:16-α – hydroxyestrone ratio, and therefore has anti- carcinogenic potential.xx[xx] xxi[xxi] Young broccoli sprouts contain 30 to 50 times the amount of isothiocyanates found in mature broccoli heads. To cut the risk of cancer in half, experts suggest consuming 2 pounds of broccoli and similar cruciferous vegetables a week. However, with the potency of broccoli sprouts, the individual would need to consume only 1 ounce of sprouts to get the same benefit.xxii[xxii] Fruit and vegetable fiber also possesses a strong significant inverse association with breast cancer risk. xxiii[xxiii] xxiv[xxiv]

The rationale for the benefit of dietary fiber in breast cancer risk reduction includesxxv[xxv]:

1. A high fiber diet reduces circulating estrogens by reducing enterohepatic recirculation of estrogen.xxvi[xxvi]
2. Many plants and vegetables contain isoflavones and lignans which are capable of being converted into weak estrogens in the bowel that may compete with estrogen binding sites.
3. A high fiber diet is generally not associated with obesity.
4. A high fiber diet usually has a lower content of fat and a higher content of antioxidant vitamins, which may protect against breast cancer.
5. Diets rich in fiber and complex carbohydrates can improve insulin sensitivity with associated reduction in circulating estrogen levels.

Xenoestrogens – “Endocrine Disruptors”

DDT, polychlorinated biphenyls and other chlorinated organic are xenobiotics that alter the body’s own production and metabolism of estrogen. The list of ubiquitous xenoestrogens includes insecticides such as DDT and methoxychlor, synthetic estrogens, aromatic hydrocarbons and breakdown components of plastics and a common weed killer Atrazine. Potentially harmful xenoestrogens also include gasoline, car emissions, synthetic estrogens and antidepressive drugs. xxvii[xxvii] xxviii[xxviii]

Medical Estrogens

Estrogen Replacement Therapy (ERT) for menopausal women increases risk for women aged 60 to 64 xxix[xxix] Oral contraceptives slightly increase the risk of having breast cancer diagnosed.xxx[xxx] The data shows that the relationship between oral contraceptives and breast cancer in younger women appears to have a biological basis rather than an artifact or result of bias xxxi[xxxi] There is a new class of medical estrogens called selective estrogen receptor modulators (SERM) that act like phytoestrogens and may reduce breast cancer by up to 50%, but, unlike soy products and other vegetable phytoestogens, SERMs may induce cancer of the ovary.xxxii[xxxii] Raloxifene (Evista) is the first drug in this class to reach the market.

Dietary Fat & Eicosanoids

Data regarding the relationship to fat in the diet to breast cancer has been inconsistent.xxxiii[xxxiii]

xxxiv[xxxiv] Studies have suggested high intakes of dietary fat result in higher levels of estrogens.xxxv[xxxv]

It is also possible that industrial chemicals (antibiotics, hormones or pesticides) contaminating meat are the culprits.xxxvi[xxxvi] xxxvii[xxxvii] xxxviii[xxxviii] It also appears that some types of fat – particularly fish oil and olive oil are protective against breast cancer,xxxix[xxxix] while animal fatsxl[xl] and polyunsaturated vegetable oils promote breast cancer.xli[xli] Again, Omega-3 fatty acids – mainly fish oil – suppress breast cancer.xlii[xlii] There is an inverse relationship between the incidence of breast cancer and the level of fish consumption, which suggests a role for omega-3 fatty acids in the prevention of breast cancer.xliii[xliii] xliv[xliv] xlv[xlv]

Fats produce chemicals called Eicosanoids in the body. Some Eicosanoids promote breast cancer, while others prevent it. This is why some fats, like red meat fats (so called –saturated fats), promote breast cancer, while Omega-3 fats protect. Interestingly, Aspirin and other anti-inflammatory drugs influence the metabolism of fats into Eicosanoids and can prevent breast cancer.xlvi[xlvi] In evaluating 511 breast cancer patients compared to 1,534 control subjects, women using nonsteroidal anti- inflammatory medications at least 3 times a week for more than 1 year had an odds ratio of .66 (that is – a 34% reduction). There were similar odds ratios for the use of ibuprofen and aspirin.xlvii[xlvii] Aspirin also reduces the risk of heart attack, and some kinds of stroke through the same chemistry; however, it increases the risk of bleeding.

Insulin & Syndrome – X

Americans are becoming progressively obese because of diet and sedentary lifestyle. This is a risk factor for a wide variety of diseases including breast cancer.xlviii[xlviii] Increased body mass results in increased insulin levels. This is called “syndrome-x.” Insulin appears to trigger breast cancer. The fattest third have a 1.9-fold higher risk of dying from breast cancer than the thinnest third.xlix[xlix] The epidemic of obesity is a complex social phenomenon, related to sedentary lifestyle, decreased fiber consumption, decreased fruit and vegetable consumption and increased “junk food” consumption. Breast cancer risk is just the tip of the iceberg!l[l]

Antioxidants

Because human being breathe oxygen, using it to “burn” fuel for energy, we are vulnerable to oxidative damage from the “sparks” (free radicals), that are an inevitable consequence of this chemistry. Free radicals are a major cause of aging, and through damaging DNA are major causes of breast cancer.

Life on earth depends on antioxidants, which “scavenge” free radicals and dispose of them safely. Our bodies have several built in anti-oxidant systems, which require nutritional factors to function properly. Some of these factors are vitamins, some are minerals, and some are other chemicals found chiefly in fruits and vegetables. There have been important observations regarding the protective effects against breast cancer for Carotenoids (from carrots and other vegetables), Retinol (Vitamin A) and Vitamin E.li[li] lii[lii] liii[liii] Vitamin C intake has a strong significant inverse association with breast cancer risk.liv[liv] Selenium in the range of 1.00-1.21 umol/L showed a significant preventive effect.lv[lv]

While taking vitamins may confer some protection from breast cancer, it should be emphasized that a wide variety of plant-based foods may be more important. Green Tea – current studies show an inverse association between green tea consumption and the number of axillary lymph node mets, as well as decreased recurrence of stage I and II breast cancer.lvi[lvi] Limonene (from lime and other citrus fruits) – in a rat model – caused complete regression of both mammary cancers.lvii[lvii] Flavonoids are polyphenolic antioxidants that occur naturally in fruits, vegetables and in beverages such as tea and wine. Many of them are scavengers of free radicals, antioxidants, chelating agents, and modifiers of enzymatic and other biological functions.lviii[lviii] Silymarin, a flavonoid antioxidant, has anticarcinogenic effects in human breast cancerlix[lix] Carotenoids (beta-cryptoxanthin, lycopene, and lutein/zeaxanthin) may protect against breast cancerlx[lx].

Other micronutrients

Vitamin D

An ecological study showed a strong inverse correlation between breast cancer mortality in the United States and ultraviolet sunlight, suggesting low vitamin D levels may play a part in breast cancer.lxi[lxi] Garlic has considerable evidence supporting its anticancer effect. The chemo preventive potential of garlic in inhibiting tumor genesis lies in the presence of organosulfur compounds such as diallylsulfide, diallydisulfide and diallylpolysulfides, thiosulfinates, sulfoxides, S- allylcysteine.lxii[lxii]

Alcohol consumption is clearly associated with breast cancer, while Folate (a B vitamin) reduces this risk. The Nurses’ Health Study of 88,000 women for 16 years, revealed 3,483 incident cases of invasive breast cancer. There was a direct association with breast cancer and the number of drinks consumed. One drink per night (such as wine) increased risk by 50%, two drinks doubled risk, however, folate consumption (such as in multi-vitamins and leafy green vegetables) mitigated this risk as well as the risk of colon cancer and coronary heart disease. lxiii[lxiii] .

Lactation

As mentioned previously, the longer a woman breast feeds, the lower her risk of breast cancer.lxiv[lxiv]

Tobacco

The odds ratio of breast cancer for ever active smokers compared to women who were unexposed to either passive or active smoke was 2.2 for an average lifetime consumption of 1 to 9 cigarettes per day, 2.7 for 10 to 19 cigarettes per day and 4.6 for 20 or more cigarettes per day. The odds ratio was 3.2 among passive smokers who were exposed for an equivalent of 2 hours per day for 25 years. Active and passive exposure to tobacco smoke may increase the risk to breast cancer.lxv[lxv]

Stress

In evaluating 119 consecutive women between 27 years of age who were referred for biopsy of suspicious lesions, 41 were diagnosed as having malignant disease. After adjusting for variables, severe life events increased the risk to breast cancer with an odds ratio of 11.6. There appears to be an etiologic association between life stress and breast cancer. lxvi[lxvi] Moreover, support groups are more beneficial to breast cancer patients than chemotherapy.lxvii[lxvii] There may be some specific psychodynamic issues related to breast cancer.lxviii[lxviii]

To Prevent Breast Cancer

• Don’t smoke (and don’t tolerate second hand smoke)

• Minimize exposure to toxic chemicals and unnecessary drugs

•Breast feed

• Work for the environment

• Deal with Stress (such as meditation)

• Get mammograms (particularly if your between 50 – 70 years of age)

• Moderate alcohol consumption, and if you do drink- take folic acid supplements (400 – 800 micrograms per day or enough to keep homocysteine level low)

• Exercise regularly

• Eat your Veggies (and Fruits) (5 – 10 servings per day )

• Eat Fiber (soluble fiber like bran, and in soluble fiber like fruits and veggies)

• Reduce Animal Fats, minimize Trans-fats (hydrogenated) increase Ω-3 fats (fish and flax) &amp Ω-9 fats (olive oil)

• Multi-vitamin / Multi-mineral supplement

• Eat Phytoestrogens every day – Soy, Apples, Rhubarb, Carrots, Pomegranate seeds, Dates, Onions, Radishes, Cucumbers, Peas, Cabbage, Legumes & Hops

• Eat Cruciferous vegetables every day (and other detoxifying foods) – Broccoli, Cabbage, Cauliflower, Brussels Sprouts, Onions, Garlic

References

i[i] Hulka, Barbara, S. and Stark, Azadeh, T., The Lancet, September 30, 1995;346:883-887.

ii[ii] Congressman David Obey in “The Politics of Cancer Revisited” see V (below)

iii[iii] H.M. Menck, et al “Industrial Air Pollution: Possible Effect on Lung Cancer” Science 183 (1974)

iv[iv] Hulka, Barbara, S. and Stark, Azadeh, T., The Lancet, September 30, 1995;346:883-887.

v[v] T J Mason & F W McKay, “:US Cancer Mortality by County, 1950-1969” DHEW Publication (NIH), 1973

vi[vi] R Hoover, T Mason, et al. “Geographic Pattern of Cancer Mortality in the US in “Person at High Risk of Cancer” New York: Academic Press 1975

vii[vii] . “Breast Cancer: Cause and Prevention”, Hulka, Barbara, S. and Stark, Azadeh, T., The Lancet, September 30,1995;346:883-887.

viii[viii] American Cancer Society “Cancer, Facts and Figures – 1997

ix[ix] “Perceptions of Breast Cancer Risk and Screening Effectiveness in Women Younger Than 50 Years of Age”, Black, William C., et al, Journal of the National Cancer Institute, May 17, 1995;87(10):720-726.

x[x] “Breast Cancer Screening With Mammography: Overview of Swedish Randomized Trials”, Nystrom, Lennarth, et al, The Lancet, April 17, 1993;341(8851):973-978

xi[xi] Salzman P, et al. Cost-effectiveness of extending screening mamography guidelines to women 40 to 49 years of age. Ann Intern Med 1997; 127:955-65.

xii[xii] S E Epstein, “The Politics of Cancer Revisited” East Ridge Press, Freemont Center NY 1998

xiii[xiii] “Nutritional, Socioeconomic, and Reproductive Factors in Relation to Female Breast Cancer Mortality: Findings From A Cross-National Study,” Hebert, James, R., Sc.D. and Rosen, Alicia, M.S., R.D., Cancer Detection and Prevention, 1996;20(3):234-244.

xiv[xiv] “Nutrition and Breast Cancer”, Boyd, Norman, The Journal of the National Cancer Institute, January 6, 1993;85(1):6-7.

xv[xv] “Foods That May Prevent Breast Cancer: Studies Are Investigating Soybeans, Whole Wheat and Green Tea Among Others”, Primary Care and Cancer, February 1994;14(2):10-11.

xvi[xvi] “Nutrition and Breast Cancer,” Hunter, David, J. and Willett, Walter, C., Cancer Causes and Control, 1996;7:56-68

xvii[xvii] . “Meta-Analysis: Dietary Fat Intake, Serum Estrogen Levels, and the Risk of Breast Cancer,” Wu AH, et al, J Natl Cancer Inst, March 17, 1999;91(6):529-534.

xviii[xviii] “Conferences Point to Growing Concern About Possible Links Between Breast Cancer, Environment,” Robson, Barbara, Canadian Medical Association Journal, April 15, 1996;154(8):1253-1255.

xix[xix] “Case-control study of phyto-estrogens and breast cancer” Ingram, et al, Lancet 10/4/97

xx[xx] “Effects of Dietary Broccoli on Human Drug Metabolizing Activity,” Kall, Morten A., et al, Cancer Letters, 1997;114:169-170

xxi[xxi] “Effects of Dietary Broccoli on Human In Vivo Drug Metabolizing Enzymes: Evaluation of Caffeine, Estrone and Chlorzoxazone Metabolism,” Kall, Morten, A., et al, Carcinogenesis, 1996;17(4):793-799

xxii[xxii] “Cancer and Broccoli,” Nutrition Week, September 19, 1997;27(36):7/New York Times, September 16, 1997;A14

xxiii[xxiii] Diet and Breast Cancer in Shanghai and Tianjin, China”, Yuan, J.M., et al, British Journal of Cancer, 1995;71:1353-1358. xxiv[xxiv] Dietary Fiber, Vitamins A, C and E and the Risk of Breast Cancer: A Cohort Study”, Rohan, Thomas E., et al, Cancer Causes and Control, 1993;4:29-37.

xxv[xxv] “Can Supplementary Dietary Fiber Suppress Breast Cancer Growth?” Stoll, B., A., et al, British Journal of Cancer, 1996;73:557-559.

xxvi[xxvi] Diet, Hormones and Cancer”, Rose, David P., Annual Review of Public Health, 1993;14:1-17

xxvii[xxvii] “Conferences Point to Growing Concern About Possible Links Between Breast Cancer, Environment,” Robson, Barbara, Canadian Medical Association Journal, April 15, 1996;154(8):1253-1255.

xxviii[xxviii] . “Can Environmental Estrogens Cause Breast Cancer? The Authors of a Provocative Hypothesis Spell Out Their Reasons For Suspecting That Hormonal-Mimicking Chemicals in The Environment Contribute to Many Unexplained Cases of Breast Cancer”, Davis, Devra Lee and Bradlow, H. Leon, Scientific American, October, 1995;166-172.

xxix[xxix] “Breast Cancer and Hormonal Supplements in Postmenopausal Women”, McPherson, Klim, British Medical Journal, September 16, 1995.

xxx[xxx] “Breast Cancer and Hormonal Contraceptives: Collaborative Reanalysis of Individual Data on 53,297 Women With Breast Cancer and 100,239 Women Without Breast Cancer From 54 Epidemiological Studies,” Collaborative Group on Hormonal Factors in Breast Cancer, The Lancet, June 22, 1996;347:1713-27

xxxi[xxxi] Brinton, Louise A., et al, Journal of the National Cancer Institute, June 7, 1995;87(11):827-835. “Oral Contraceptives and Breast Cancer Risk Among Younger Women

xxxii[xxxii] S E Epstein, “The Politics of Cancer Revisited” East Ridge Press, Freemont Center NY 1998. Page 489

xxxiii[xxxiii] Dietary Fat, Calories and the Risk of Breast Cancer in Postmenopausal Women: A Prospective Population-Based Study”, Barrett-Connor, Elizabeth, M.D. and Friedlander, Nancylee J., Ph.D., Journal of the American College of Nutrition, 1993;12(4):390-399.

xxxiv[xxxiv] “A Prospective Cohort Study on Dietary Fat and Risk of Postmenopausal Breast Cancer”, Van Den Brandt, Piet, et al, Cancer Research, January 1, 1993;53:75-82.

xxxv[xxxv] “Diet, Hormones and Cancer”, Rose, David P., Annual Review of Public Health, 1993;14:1-17

xxxvi[xxxvi] “Diet Low in Fat May Reduce Areas of Mammographic Densities,” Primary Care & Cancer, January, 1998;13. 29164

xxxvii[xxxvii] Diet and Breast Cancer in Shanghai and Tianjin, China”, Yuan, J.M., et al, British Journal of Cancer, 1995;71:1353-1358

xxxviii[xxxviii] . “Cohort Studies of Fat Intake and the Risk of Breast Cancer – A Pooled Analysis,” Hunter, David, J., M.B., B.S., et al, New England Journal of Medicine, February 8, 1996;334:356-361.

xxxix[xxxix] . “Cyclo-oxygenase 2 and Breast Cancer Prevention: Non-steroidal Anti-Inflammatory Agents Are Worth Testing in Breast Cancer,” Vainio H and Morgan G, BMJ, September 26, 1998;317:828.

xl[xl] “Effects of a Very Low Fat, High Fiber Diet on Serum Hormones and Menstrual Function: Implications For Breast Cancer Prevention”, Bagga, Dilprit, Ph.D., et al, Cancer, December 15, 1995;76(12):2491-2496

xli[xli] “The Role of Fatty Acids and Eicosanoid Synthesis Inhibitors in Breast Cancer”, Noguchi, Masakuni, M.D., Oncology, 1995;52:265-271

xlii[xlii] “The Role of Fatty Acids and Eicosanoid Synthesis Inhibitors in Breast Cancer”, Noguchi, Masakuni, M.D., Oncology, 1995;52:265-271

xliii[xliii] “The Role of Fatty Acids and Eicosanoid Synthesis Inhibitors in Breast Cancer”, Noguchi, Masakuni, M.D., Oncology,1995;52:265-271

xliv[xliv] “Fatty Acid Composition of Breast Adipose Tissue in Breast Cancer Patients and in Patients With Benign Breast Disease”, Zhu, Z.R., et al, Nutrition and Cancer, 1995;24(2):151-160.

xlv[xlv] . “Dietary Omega-3 Polyunsaturated Fatty Acids and Breast Cancer,” Cave, William, T., Jr., M.D., Nutrition, Suppl.:1996;12(1):S30-S41

xlvi[xlvi] . “Cyclo-oxygenase 2 and Breast Cancer Prevention: Non-steroidal Anti-Inflammatory Agents Are Worth Testing in Breast Cancer,” Vainio H and Morgan G, BMJ, September 26, 1998;317:828.

xlvii[xlvii] . “Nonsteroidal Antinflammatory Drugs and Breast Cancer,” Harris, Randall, E., et al, Epidemiology, March, 1996;7(2):203-205

xlviii[xlviii] “Body Weight: Estimation of Risk for Breast and Endometrial Cancers,” Ballard-Barbash, Rachel, et al, American

Journal of Clinical Nutrition, 1996;63(Suppl.):437S-41S.

xlix[xlix] . “Breast Cancer Survival for Postmenopausal Women Who Are Less Overweight and Eat Less Fat”, Zhang, Shumin, M.D., et al, Cancer, July 15, 1995;76(2):275-283.

l[l] . “Nutrition and Breast Cancer Risk: Can an Effect Via Insulin Resistance Be Demonstrated?” Stoll, Basil, A., et al, Breast Cancer Research and Treatment, 1996;38:239-246.

li[li] “Carotenoids, Retinol, and Vitamin E and Risk of Proliferative Benign Breast Disease and Breast Cancer”, London, Stephanie, et al, Cancer Causes and Control, 1992;3:503-512

lii[lii] Dietary Fiber, Vitamins A, C and E and the Risk of Breast Cancer: A Cohort Study”, Rohan, Thomas E., et al, Cancer Causes and Control, 1993;4:29-37.

liii[liii] “A Prospective Study of the Intake of Vitamins C, E and A and the Risk of Breast Cancer”, Hunter, David J., M.B., et al, New England Journal of Medicine, July 22, 1993;329(4):234-240.

liv[liv] Dietary Fiber, Vitamins A, C and E and the Risk of Breast Cancer: A Cohort Study”, Rohan, Thomas E., et al, Cancer Causes and Control, 1993;4:29-37.

lv[lv] “Levels of Selenium in Plasma and Glutathione Peroxidase in Erythrocytes and the Risk of Breast Cancer: A Case-Control Study”, Hardell, Lennart, et al, Biological Trace Element Research, 1993;36:99-108.

lvi[lvi] Komori A, Yatsunami J, Okabes S, et al. Anticarcinogenic activity of green tea polyphenols. Jpn J Clin Oncol 1993:23:186-290.

lvii[lvii] “Limonene-Induced Regression of Mammary Carcinomas”, Haag, Jill D., et al, Cancer Research, 1992;52:4021-4026

lviii[lviii] “Role of Chemopreventers in Human Diet”, Stavric, Bozidar, Clinical Biochemistry, 1994;27(5):319-332.

lix[lix] Zi, et al Clion Cancer Res 1998;3;1055-1064

lx[lx] Dorgan et al, Cancer Causes Control 1998;9:89-97

lxi[lxi] Breast Cancer: Nutritional Factors”, Hunter, David and Trichopoulos, Dimitrios, The Lancet, October 10, 1992;340:905.

lxii[lxii] “Role of Chemopreventers in Human Diet”, Stavric, Bozidar, Clinical Biochemistry, 1994;27(5):319-332.

lxiii[lxiii] Shumin Zhang, M.D., Sc.D. Research Associate, Department of Nutrition Harvard School of Public Health 665 Huntington Avenue Boston, MA 02115 (617) 432-2855 / (617) 432-2435 FAX “A Prospective Study of Folate Intake and the Risk of Breast Cancer,” JAMA, May 5, 1999;281(17):1632-1637.

lxiv[lxiv] “Breast Cancer and Lactation History in Mexican Women,” Romieu, Isabelle, et al, American Journal of Epidemiology, 1996;143(6):543-52.

lxv[lxv] – “Relation of Breast Cancer With Passive and Active Exposure to Tobacco Smoke,” Morabia, Alfredo, et al, American Journal of Epidemiology, 1996;143(9):918-927.

lxvi[lxvi] “Adverse Life Events and Breast Cancer: Case-Controlled Study,” Chen, C., C., et al, British Medical Journal, December 9, 1995;311:1527-1530.

lxvii[lxvii] Spiegel, D, in: Healing and the Mind, Bill Moyers editor

lxviii[lxviii] LeShan L & Worthington RE. Loss of cathexes as a common psychodynamic charcteristic of cancer patients. Psychological Reports. 1956; 2:183-93.

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