Breast Cancer Prevention

The natural, alternative approach to cancer treatment and prevention can’t make money for an entity because natural substances cannot be patented.  Therefore, little interest in their exploration and development has emerged.  Without funding, classic studies can’t be performed on a large scale.  Yet, there are a few brave souls who delve into the bright possibilities (hope) of promoting natural substances to heal disease, whether they come directly from foods or indirectly via sensible supplementation.   All the while, common elements that traditional and integrative medicine share are the promotion of health by altering one’s lifestyle and using known factors to predict risk of disease.

There are so many components tied to the onset of cancer that it’s hard to tell which have the strongest influence on prevention or promotion.  In 2009, scientists at the California Pacific Medical Center Research Institute examined a few of these factors and concluded that screening for breast cancer has a positive influence on outcomes, while certain lifestyle interventions may enhance the potential to prevent it.  Estimating breast cancer risk is not a cut and dry matter, but breast density and estradiol levels are strongly associated with disease.  (Cummings. 2009)  Exercise, weight reduction, low-fat diet, and reduced alcohol use are matters to consider because all are associated with reduced risk.  Post-menopausal women appear to fare poorly from breast density factors and are urged to consider chemoprevention if found to be at high risk after all parameters are evaluated.  (Ibid.)  Mammography and self-examination reduce breast cancer mortality by a significant amount, especially among women between ages forty and seventy-four.  (Humphrey. 2002)  Tamoxifen and raloxifene, used for chemoprevention, are not without their side effects, ranging from vision changes to chest pain to hot flashes.  What about alternatives?

Prevention of obesity, or losing weight if already a problem, is essential to addressing breast cancer, both as a risk and as an established disease.  The relationship is complicated, but the association is there.  Body mass index, weight, weight gain, and waist-to-hip ratio have all been positively tied to breast cancer risk in post-menopausal women, though the tie-in is not so strong among pre-menopausal women.  (Carmichael. 2006)  Nonetheless, obesity at the time of diagnosis is significant as a poor prognostic factor.  Weight management as preventive cannot be stressed strongly enough.  Poor dietary choices are the main cause of weight gain, either eating the wrong foods or too much of the right ones.  Eating more plant-based protein and lots of fruits and vegetables, being adequately hydrated, eliminating or limiting simple carbohydrates and sugars, avoiding food preservatives and artificial colors where practicable, and enjoying nuts and seeds are strongly recommended practices.  Look at this as an abundance model rather than a deprivation model.

Certain enzymes are entailed in the incidence and progress of cancer, including breast and other soft tissues.  Their names include aromatase, telomerase, and one simply named AKT.  Inhibition of these substances is one of the goals of cancer researchers, some of whom have found that a food component termed indole-3-carbinol (I3C) is such an inhibitor.  Produced by the Brassica family of vegetables—including Brussels sprouts, cabbages, broccoli, etc.—I3C inhibits cell proliferation and induces cell death (apoptosis) in abnormal breast, prostate, and colon tissues.  What’s more, laboratory-enhanced analogues of I3C were found to be more potent at downregulating AKT in particular and other enzymes in general.  (Kim. 2011)  Additional findings indicated that cell cycle arrest of estrogen-responsive breast cancer lines was initiated by cruciferous vegetable constituents.  (Marconett. 2011)  Under acidic conditions, such as exist in the stomach, I3C is potentiated to its most active metabolite, di-indolylmethane (DIM), the main factor responsible for biological effects inside the body and resulting suppression of cancer cell proliferation.  (Aggarwal.  2005)  I3C supplements are available.

When cells are overstressed and their innate anti-oxidant capabilities are taxed, carcinogenesis may occur.  Several phytochemicals, derived from plants that include herbs and spices and not just fruits and vegetables, have demonstrated excellent chemoprotective characteristics.  Besides the crucifers cited, the simple herb cardamom, a member of the ginger family, shows promise as a provider of DIM to be applied to prophylaxis and treatment not only in carcinogenesis, but also in atherosclerosis and HPV infection.  (Acharya. 2010)  Another Brassica component with breast cancer protection properties is benzyl-isothiocyanate, a material that has exhibited anti-proliferation capability in both breast and pulmonary tissue.  (Kim.  2011)

One of the nutrients in sore supply in humans is iodine, a mineral that has been taken for granted since it appeared as a salt additive years ago.  Iodine deficiency affects almost two billion people on earth and is the number one preventable cause of mental handicap.  With the advent of other salts for culinary use, iodine has been relegated to the back burner.  The consumption of iodine-rich foods, as exemplified by those who eat seaweed as part of their traditional cuisine, does not appear to cause toxicity, but instead may reveal itself as an important element in maintaining breast tissue architecture and function.    (Patrick.  2008)  Seaweed as a dietary preference in Japan, for example, may be associated with the very low incidence of malignant and benign breast disease.  Therapeutic administration of iodine in the presence of selenium has shown anti-oxidant as well as anti-proliferative character.  (Cann.  2000)  Mexican investigators have discovered iodine to be useful as adjuvant treatment in breast cancer therapy, contributing to the integrity of normal mammary tissue.  (Aceves.  2005)  Kelp, yogurt, eggs, strawberries, and seafoods are good food sources.  Revisiting iodized salt is a prudent option.

In active disease, cancer cells may exhibit resistance to radiation.  It is this feature that has led researchers to find a way to make these stubborn cells less so.  Vitamin K, as a newly-synthesized form of K2 (VK2), not only restored radiation sensitivity, but also inhibited growth of cancer cells.  But not just in breast cancer lines.  Lung and colon cancers also responded.  The formation of selective reactive oxygen species, affecting only the cancerous but not the healthy cells, seems to be the driving mechanism.  (Amalia.  2010)   Vitamin K3, a synthetic form also called menadione, is not generally used to make supplements due to its toxic nature, but has been used successfully to alter the course of breast cancer treatment.  (Akiyoshi.  2009)

We don’t think of rest as being part of the armamentarium in treating sickness, but a relationship between sleep and interruption of the circadian clock has been found to have a decided impact on cancer genesis.  When jobs and entertainment interfere with the body’s response to night-time chemical manufacture, maybe we shouldn’t be too surprised that metabolic upset occurs.  Back in the 80’s it was proposed that the increasing use of electricity to light the night could account for the global rise in breast cancer risk.  It was theorized that blindness and long sleep duration reduce risk, and shift work increases risk.

This has spawned an interest in exploring the function of circadian genes, thinking that epigenetic alterations might be causative.  Studies indicate that certain urine melatonin compounds, concentrations of luteinizing hormones, follicle stimulating hormone, and estradiol are indicators of breast cancer risk.  Though not definitive, the implications are not to be ignored.  (Stevens.  2009)  (Davis.  2006)  Getting by on four hours of sleep does a body no good.

Nutrient intake unbalances the scale in favor of breast cancer prevention.  Among the nutrients studied are vitamins B2, B3, B6, B12, folate, and the amino acid methionine.  A study of Chinese women conducted by Vanderbilt University indicates that high folate intake may reduce breast cancer risk and that the association depends on estrogen and progesterone receptor status, particularly as related to pre-menopausal women. (Shrubsole.  2011)   Earlier probes likewise found folate to be preventive in light of hormone conditions, but even more so when combined with vitamin B12.  (Wu.  1999) (Larsson.  2008)  (Lajous.  2006)  A synergy was discovered when the beneficial effect of folate was accentuated by dietary intake of methionine, vitamin B12, and B6.  (Shrubsole.  2001)  Folinic acid is a form of folate that has vitamin function equivalent to folic acid, but requires no enzymatic conversion.  Folinic acid encourages normal DNA replication and RNA transcription, and has the unique ability to reinforce drug treatment for active disease.

Xanthophylls are pigments that accompany chlorophyll in green plants, and are often identified with lutein.  Being yellow, their color is masked by chlorophyll in mature leaves.  Their job is to absorb certain wavelengths of light not gathered by chlorophyll, then to transfer that energy to the chlorophyll by ramping up electrons.  They are similar to, but not exactly like, carotenes.   Foods that contain xanthophylls have demonstrated protection against the onset of breast and lung cancers, although their claim to fame is protecting vision against both cataracts and age-related macular degeneration.  Research in this arena is somewhat limited, but recommendations for intake align with current dietary guidelines.  (Judy.  2004)  All leafy greens are sources.

Undergoing serious examination as preventive of breast cancer is curcumin, the active ingredient of turmeric.  Cancer cells treated with this polyphenol fail to proliferate and invade at normal rate by virtue of protein disruption (Zong.  2011).  Curcumin’s cytotoxicity as an anti-oxidant is dose-dependent, but its presence in the breast cancer war can’t be overlooked.  (Quiroga.  2010)

It’s been estimated that 30%-40% of all cancers can be prevented by lifestyle and dietary measures alone.  The protective elements in a cancer prevention diet may reduce likelihood of disease by more than 60%, and would favor recovery from disease as well.  (Donaldson.  2004)

Aceves C, Anguiano B, Delgado G. Is iodine a gatekeeper of the integrity of the mammary gland? J Mammary Gland Biol Neoplasia. 2005 Apr;10(2):189-96.

Acharya A, Das I, Singh S, Saha T Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis. Recent Pat Food Nutr Agric. 2010 Jun;2(2):166-77.

Aggarwal BB, Ichikawa H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle. 2005 Sep;4(9):1201-15.

Akiyoshi T, Matzno S, Sakai M, Okamura N, Matsuyama K. The potential of vitamin K3 as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway. Cancer Chemother Pharmacol. 2009 Dec;65(1):143-50.

Amalia H, Sasaki R, Suzuki Y, Demizu Y, Bito T, Nishimura H, Okamoto Y, Yoshida K, Miyawaki D, Kawabe T, Mizushina Y, Sugimura K. Vitamin K2-derived compounds induce growth inhibition in radioresistant cancer cells. Kobe J Med Sci. 2010 Sep 28;56(2):E38-49.

Cann SA, van Netten JP, van Netten C. Hypothesis: iodine, selenium and the development of breast cancer. Cancer Causes Control. 2000 Feb;11(2):121-7.

Carmichael AR. Obesity and prognosis of breast cancer. Obes Rev. 2006 Nov;7(4):333-40.

Cummings SR, Tice JA, Bauer S, Browner WS, Cuzick J, Ziv E, Vogel V, Shepherd J, Vachon C, Smith- Bindman R, Kerlikowske K. Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk. J Natl Cancer Inst. 2009 Mar 18;101(6):384-98.

Davis S, Mirick DK. Circadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in Seattle. Cancer Causes Control. 2006 May;17(4):539-45.

Michael S Donaldson Nutrition and cancer: A review of the evidence for an anti-cancer diet Nutrition Journal 2004, 3:19

Francini G, Petrioli R, Aquino A, Gonnelli S. Advanced breast cancer treatment with folinic acid, 5-fluorouracil, and mitomycin C. Cancer Chemother Pharmacol. 1993;32(5):359-64.

Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002 Sep 3;137(5 Part 1):347-60.

Kim EJ, Hong JE, Eom SJ, Lee JY, Park JH. Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. Breast Cancer Res Treat. 2011 Nov;130(1):61-71.

Judy D. Ribaya-Mercado, ScD and Jeffrey B. Blumberg, PhD, FACN Lutein and Zeaxanthin and Their Potential Roles in Disease Prevention J Am Coll Nutr December 2004 vol. 23 no. suppl 6 567S-587S

Kim DJ, Reddy K, Kim MO, Li Y, Nadas J, Cho YY, Kim JE, Shim J, Song NR, Carper A, Lubet RA, Bode AM, Dong Z. (3-Chloroacetyl)-indole, a novel allosteric AKT inhibitor suppresses colon cancer growth in vitro and in vivo Cancer Prev Res (Phila). 2011 Sep 1.

Lajous M, Lazcano-Ponce E, Hernandez-Avila M, Willett W, Romieu I. Folate, vitamin B(6), and vitamin B(12) intake and the risk of breast cancer among Mexican women. Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):443-8.

Lajous M, Romieu I, Sabia S, Boutron-Ruault MC, Clavel-Chapelon F. Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women. Cancer Causes Control. 2006 Nov;17(9):1209-13.

Larsson SC, Bergkvist L, Wolk A. Folate intake and risk of breast cancer by estrogen and progesterone receptor status in a Swedish cohort. Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3444-9.

Marconett CN, Sundar SN, Tseng M, Tin AS, Tran KQ, Mahuron KM, Bjeldanes LF, Firestone GL. Indole-3-carbinol downregulation of telomerase gene expression requires the inhibition of estrogen receptor-alpha and Sp1 transcription factor interactions within the hTERT promoter and mediates the G1 cell cycle arrest of human breast cancer cells. Carcinogenesis. 2011 Sep;32(9):1315-23

Patrick L. Iodine: deficiency and therapeutic considerations. Altern Med Rev. 2008 Jun;13(2):116-27.

Quiroga A, Quiroga PL, Martínez E, Soria EA, Valentich MA. Anti-breast cancer activity of curcumin on the human oxidation-resistant cells ZR-75-1 with gamma-glutamyltranspeptidase inhibition. J Exp Ther Oncol. 2010;8(3):261-6.

Shrubsole MJ, Jin F, Dai Q, Shu XO, Potter JD, Hebert JR, Gao YT, Zheng W. Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res. 2001 Oct 1;61(19):7136-41.

Shrubsole MJ, Shu XO, Li HL, Cai H, Yang G, Gao YT, Gao J, Zheng W. Dietary B vitamin and methionine intakes and breast cancer risk among Chinese women. Am J Epidemiol. 2011 May 15;173(10):1171-82.

Stadel BV. Dietary iodine and risk of breast, endometrial, and ovarian cancer. Lancet. 1976 Apr 24;1(7965):890-1.

Stevens RG. Working against our endogenous circadian clock: Breast cancer and electric lighting in the modern world. Mutat Res. 2009 Nov-Dec;680(1-2):106-8.

Wu K, Helzlsouer KJ, Comstock GW, Hoffman SC, Nadeau MR, Selhub J. A prospective study on folate, B12, and pyridoxal 5'-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev. 1999 Mar;8(3):209-17.

A. Zaniboni, F. Meriggi, G. Arcangeli, P. Marpicati, E. Montini, E. Simoncini and G. Marini L-folinic acid and 5-fluorouracil in the treatment of advanced breast cancer: A phase II study Ann Oncol (1993) 4 (suppl 2): S41-S43.

Zong H, Wang F, Fan QX, Wang LX. Curcumin inhibits metastatic progression of breast cancer cell through suppression of urokinase-type plasminogen activator by NF-kappa B signaling pathways. Mol Biol Rep. 2011 Sep 24.