The Integrative Treatment of Breast Cancer

The National Cancer Institute estimates that 226,870 women will be diagnosed with and 39,510 women will die of breast cancer in 2012. NCI also report that 12.38 percent of women born today (one in eight women) will be diagnosed with breast cancer some time during their lifetime¹ Yet despite these seemingly grim statistics, there are many treatment options, which have brought new hope in the fight against this disease. In fact, according to Breastcancer.org² these treatments include:

• Surgery (lumpectomy, mastectomy, and lymph node dissection)
• Chemotherapy
• Radiation therapy
• Hormonal therapy
• Targeted therapies (Herceptin, Tykerb, Avastin, Perjeta, Afinitor)
• Complementary medicine
• Drugs for treatment and risk reduction

This article will focus of the use of integrative medicine in the treatment and prevention of breast cancer. More specifically, it will focus on coenzyme Q10, soy isoflavones, indole-3-carbinol and DIM, laughter, folic acid and dietary fiber as complementary medicine therapies. Diet in general also plays an important role, and there are other viable complementary therapies as well. However, due to space limitations this article will not address diet (with the exception of fiber) and those other therapies.

Coenzyme Q10
Biochemical, biomedical and clinical research on coenzyme Q10 (CoQ10) and its relationship to treating cancer has evolved internationally over 35 years. Some interesting research published in a scientific journal in 1995 discussed three specific breast cancer patients who underwent a conventional protocol of therapy, which included 390 mg of CoQ10. In one 44-year-old patient, the numerous liver metastases “disappeared,” and no signs of metastases were found elsewhere. Another 49-year-old patient revealed no signs of tumor in the pleural cavity after six months, and her condition was excellent. A 75-year-old patient with carcinoma in one breast showed no cancer in the tumor bed or metastases after lumpectomy and 390 mg of CoQ10 daily.³

Of course it’s great to quote a few isolated cases where breast cancer patients responded well to CoQ10 therapy, but have there been positive results when CoQ10 was given to larger groups of patients? As a matter of fact, yes. Thirty-two typical patients with breast cancer, aged 32–81 years and classified ‘high risk’ because of tumor spread to lymph nodes, where studied for 18 months following the administration of a special dietary supplement program. The supplement program included a combination of antioxidants including vitamin C, vitamin E, beta-carotene, selenium, essential fatty acids, and 90 mg of CoQ10 daily. The results of the study were: 1) none of the patients died during the study period (the expected number was four); 2) none of the patients showed signs of further distant metastases; 3) quality of life was improved (no weight loss, reduced use of pain killers); 4) six patients showed apparent partial remission.⁴

Interestingly, in a subsequent follow-up study, one of the aforementioned six patients who showed partial remission had her dose increased to 390 mg daily. In one month, the tumor was no longer palpable, and in another month, mammography confirmed the absence of tumor. Another patient who had nonradical surgery still had residual tumor in the tumor bed. She was treated with 300 mg of CoQ10, and in three months was in excellent clinical condition and there was not residual tumor tissue.⁵

Soy and its isoflavones
One of the risk factors in the development of breast cancer has to do with the conversion of the estrogen hormone estradiol into the estrogen compounds 2-hydroxyestrone and 16-alphahydroxyestrone. Specifically, research suggests that conversion into 2-hydroxyestrone is associated with a reduced risk of breast cancer, while conversion into 16-alpha-hydroxyestrone is associated with an increased risk. That’s where soy isoflavones come into the picture.

The isoflavones in soybeans have been shown to have anti-cancer effects. One particular isoflavone called genistein (and possibly another called daidzein) has been proposed to contribute an important part of the anti-cancer effect of soy isoflavones. As a matter of fact, genistein in soy is considered by some researchers to be responsible for the lower rate of breast cancer observed in Asian women consuming soy. The reason for this anti-cancer effect may be that soy isoflavones increase the conversion of estradiol to 2-hydroxyestrone, but not 16-alpha-hydroxyestrone.⁶

The effect of genistein was tested in one study in five human breast cancer cell lines. Genistein inhibited the growth of each of these cancer cells⁷ Similar studies using genistein also showed significant inhibitory effects on breast cancer cells. It seems that genistein affects estrogen receptors in such a way as to prevent breast cancer growth.⁸ This estrogen altering response was also apparent in another study, which examined the influence of total soy isoflavones in six premenopausal women for one month. The result was that menstruation was delayed and cholesterol concentrations decreased 9.6 percent.⁹

Despite these positive results, there seems to be conflicting research about genistein and breast cancer. Some research suggests that genistein is beneficial, while other research suggests it may actually contribute toward the disease.¹⁰ In one study, genistein given to rats early in their lives helped reduce the incidence of mammary (breast) tumors.¹¹ However, in research where mice were implanted with human breast cancer cells, genistein seemed to promote the growth of tumors in a similar way to 16-alpha-hydroxyestrone.¹² According to one researcher, the issue really seems to be related to timing. Although there is still no universal consensus among researchers on this issue, if you want to play it safe and take a conservative position, then follow this rule of thumb: if you don’t have breast cancer, the use of soy isoflavones may help to prevent it. If you already have breast cancer, soy isoflavones may promote its growth.¹³

Indole-3-Carbinol and DIM
Indole-3-carbinol is an extremely valuable compound found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, collards, cauliflower, kale, kohlrabi, mustard greens, rapeseed, and root vegetables such as turnips and rutabagas.^14,15 While this compound has value for women and men, researchers are interested in indole-3-carbinol for its role in helping to promote healthy breast cell division and replication. Indole-3-carbinol is one of several vegetable compounds that might play such a valuable role in healthy cell division, reducing the risk of breast cancer.^16,17,18

As discussed previously, estradiol can be converted into 2-hydroxyestrone (the “good estrogen metabolite”) and 16-alpha-hydroxyestrone (the “bad estrogen metabolite”). The bad metabolite can promote cancer of the breast and cervix, whereas the good metabolite does not do this. Indole-3-carbinol gets into the act by promoting the conversion of estradiol into the good metabolite, ultimately reducing the risk of breast cancer.^{19,20,21,22,23,24} In addition, research suggests that indole- 3-carbinol has protective antioxidant properties.^25,26

When indole-3-carbinol comes in contact with stomach acid it is converted into active metabolites, including diindolylmethane (DIM).²⁷ Like indole-3-carbinol, researchers are interested in DIM for its role in helping to promote healthy cell division cell replication in breast cells, and the prevention of breast cancer.^{28,29,39,31,32} Also like indole-3-carbinol, DIM helps promote the conversion of estradiol into the good metabolite.³³ Furthermore, DIM also helps promote a healthy turnover of breast cells.³⁴

Daily dietary intake of indole-3-carbinol is typically 20– 120 mg daily, while dietary intake of DIM is typically 2–24 mg daily.^35,36,37,38 However, research has shown that indole-3-carbinol and DIM’s ability to help prevent breast cancer occurs at daily levels of 200–300 mg and 100–200 mg, respectively. If supplementing, therefore, it may make sense to utilize these levels of indole-3-carbinol and DIM.

Laughter therapy
Laughter has positive, quantifiable effects on certain aspects of health.³⁹ Research has demonstrated that a number of physiological changes take place when we laugh, including the release of endorphins which suppress pain,^40,41,42 increases in immune cell production (e.g., NK cell activity,⁴³ antibodies), a dramatic reduction in the stress hormone cortisol, and a decrease in the hormone epinephrine, which plays a role in hypertension and heart failure.⁴⁴ More specific to the topic of this article, researchers tested the effectiveness of laughter therapy on levels of depression, quality of life, resilience and immune responses in 37 breast cancer survivors (16 subjects in the experiment group, 21 in the control group) who underwent chemotherapy and radiation therapy.⁴⁵ They found that laughter therapy was effective in increasing the quality of life and resilience in breast cancer survivors.

Folic acid and alcohol
Moderate alcohol intake has been associated with increased risk of breast cancer in women in several studies. Consequently, it is significant that two different studies suggest that women who regularly consume alcohol can decrease their risk of breast cancer by increasing their intake of folic acid.^46,47,48 In one study of more than 88,000 nurses, women consuming at least one alcoholic drink per day cut their risk of breast cancer in half with a daily intake of at least 600 mcg folic acid, while those with an intake of less that 300 mcg of folic acid did not have the same reduction in risk.⁴⁹

Dietary fiber
Research has suggested a protective effect of dietary fiber on breast cancer risk. For example, risk of breast cancer in premenopausal women was reduced with an increase in fiber intake in a prospective cohort study in the UK.⁵⁰ In Sweden, a prospective cohort study demonstrated that postmenopausal women with the fiber intakes averaging about 26 grams daily had 40 percent lower risk of breast cancer than women with the fiber intakes averaging about 13 grams daily;⁵¹ and those with the highest fiber and lowest fat intakes had the very lowest risk of breast cancer. A 13 percent lower risk of all forms of breast cancer was seen with the highest intakes of dietary fiber (with a mid-range of 26 grams day) compared to the lowest intakes (midrange of 11 grams) in a U.S. prospective study of more than 185,000 postmenopausal women.⁵² In 2011 a meta-analysis of ten prospective cohort studies found a modest, 11 percent lower risk of breast cancer in women with the highest intakes of dietary fiber.⁵³ Smaller, short-term intervention trials in premenopausal and postmenopausal women found that diets that were low-fat and high-fiber (25–40 grams daily) increasing the conversion of estradiol into the good estrogen metabolites.^54,55

Conclusion
The prevention and treatment of breast cancer requires a multifaceted approach. This may include the integrative use of conventional and complementary therapies. The use of the complementary medicine therapies discussed in this article may have a place in a comprehensive, physician-supervised program of breast cancer care.

1. Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2009_pops09/, based on November 2011 SEER data submission, posted to the SEER web site, 2012.
2. Treatment & Side Effects. Breastcancer.org. Page last modified on: April 29, 2012. Retrieved September 13, 2012 from http://www.breastcancer.org/treatment/.
3. Lockwood K, Moesgaard S, Yamamoto T, Folkers K. Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 1995; 212(1):172–7.
4. Lockwood K, Moesgaard S, Hanioka T, et al. Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med 1994;15(Suppl):s231–40.
5. Lockwood K, Moesgaard S, Folkers K. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun 1994; 199(3):p1504–8
6. Lu LJ, Cree M, Josyula S, Nagamani M, Grady JJ, Anderson KE. Increased urinary excretion of 2-hydroxyestrone but not 16-alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones. Cancer Res. 2000 Mar 1;60(5):1299–305.
7. Pagliacci MC, Smacchia M, Migliorati G, Grignani F, Riccardi C, Nicoletti I. Growth inhibitory effects of the natural phyto oestrogen genistein in MCF 7 human breast cancer cells. Eur J Cancer 1994; 30A(11):1675–82.
8. Wang TT, Sathyamoorthy N, Phang JM. Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis 1996; 17(2) p 271–5.
9. Cassidy A, Bingham S, Setchell KD. Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr 1994; 60(3):333–40.
10. Stopper H, Schmitt E, Kobras K. Genotoxicity of phytoestrogens. Mutat Res 2005; 574(1-2):139–55.
11. Helferich W. Effect of Genistein on Growth of Human Breast Cancer Cells. IN Phytochemicals As Bioactive Agents. Bidlack WR, Omaye ST, Meskin MS, Topham DKW (Eds.). Lancaster, Pennsylvania: Technomic Publishing; 2000:151–160.
12. Helferich W. Effect of Genistein on Growth of Human Breast Cancer Cells. IN Phytochemicals As Bioactive Agents. Bidlack WR, Omaye ST, Meskin MS, Topham DKW (Eds.). Lancaster, Pennsylvania: Technomic Publishing; 2000:151–160.
13. Helferich W. Effect of Genistein on Growth of Human Breast Cancer Cells. IN Phytochemicals As Bioactive Agents. Bidlack WR, Omaye ST, Meskin MS, Topham DKW (Eds.). Lancaster, Pennsylvania: Technomic Publishing; 2000:151–160.
14. Natl Inst Health, Natl Inst Environmental Health Sci. Indole-3-carbinol. Available at: http://ntp-server.niehs.nih.gov
15. Balk JL. Indole-3-carbinol for cancer prevention. Altern Med Alert 2000; 3:105–7.
16. Wong GY, Bradlow L, Sepkovic D, et al. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl 1997;28-29:111–6.
17. Grubbs CJ, Steele VE, Casebolt T, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res 1995;15:709–16.
18. Yuan F, Chen DZ, Liu K, et al. Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res 1999;19:1673–80.
19. Michnovicz JJ. Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol. Int J Obes Relat Metab Disord 1998;22:227–9.
20. Michnovicz JJ, Bradlow HL. Induction of estradiol metabolism by dietary indole-3-carbinol in humans. J Natl Cancer Inst 1990;82:947–9.
21. Bradlow HL, Michnovicz J, Telang NT, Osborne MP. Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis 1991;12:1571–4.
22. Grubbs CJ, Steele VE, Casebolt T, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res 1995;15:709–16.
23. Kojima T, Tanaka T, Mori H. Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol. Cancer Res 1994;54:1446–9.
24. Yuan F, Chen DZ, Liu K, et al. Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res 1999;19:1673–80.
25. Telang NT, Katdare M, Bradlow HL, et al. Inhibition of proliferation and modulation of estradiol metabolism: novel mechanisms for breast cancer prevention by the phytochemical indole-3-carbinol. Proc Soc Exp Biol Med 1997;216:246–52.
26. Bradlow HL, Sepkovic DW, Telang NT, Osborne MP. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann N Y Acad Sci 1999;889:204–13.
27. Ibid.
28. Riby JE, Chang GHF, Firestone GL, Bjeldanes LF. Ligand-independent activation of estrogen receptor function by 3,3’-diindolylmethane in human breast cancer cells. Biochem Pharmacol 2000;60:167–77.
29. McDougal A, Gupta MS, Ramamoorthy K, et al. Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane. Cancer Lett 2000;151:169–79.
30. Chen I, McDougal A, Wang F, Safe S. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis 1998 Sep;19:1631–9.
31. Ge X, Yanni S, Rennert G, et al. 3’3-diindolylmethane induces apoptosis in human cancer cells. Biochem Biophys Res Commun 1996;228:153–8.
32. Chen I, Safe S, Bjeldanes L. Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. Biochem Pharmacol 1996;51:1069–76.
33. Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer 2004;50(2):161–7.
34. Ge X, Yanni S, Rennert G, et al. 3’3-diindolylmethane induces apoptosis in human cancer cells. Biochem Biophys Res Commun 1996;228:153–8.
35. Natl Inst Health, Natl Inst Environmental Health Sci. Indole-3-carbinol. Available at: http://ntp-server.niehs.nih.gov
36. Natl Inst Health, Natl Inst Environmental Health Sci. Indole-3-carbinol. Available at: http://ntp-server.niehs.nih.gov
37. Balk JL. Indole-3-carbinol for cancer prevention. Altern Med Alert 2000; 3:105-7.
38. Riby JE, Chang GHF, Firestone GL, Bjeldanes LF. Ligand-independent activation of estrogen receptor function by 3,3’-diindolylmethane in human breast cancer cells. Biochem Pharmacol 2000;60:167-77.
39. Mora-Ripoll R. The therapeutic value of laughter in medicine. Altern Ther Health Med. 2010;16(6):56-64.
40. Miller M, Fry WF. The effect of mirthful laughter on the human cardiovascular system. Med Hypotheses. 2009;73(5):636-9.
41. Weisenberg M, Tepper I, Schwarzwald J. Humor as a cognitive technique for increasing pain tolerance. Pain. 1995;63(2):207-12.
42. Liebertz C. A Healthy Laugh. Scientific American 2005 Sept 21; retrieved January 16, 2012 from http://www.scientificamerican.com/article.cfm?id=a-healthy-laugh.
43. Bennett MP, Zeller JM, Rosenberg L, McCann J. The effect of mirthful laughter on stress and natural killer cell activity. Altern Ther Health Med. 2003;9(2):38-45.
44. Liebertz C. A Healthy Laugh. Scientific American 2005 Sept 21; retrieved January 16, 2012 from http://www.scientificamerican.com/article.cfm?id=a-healthy-laugh
45. Cho EA, Oh HE. [Effects of laughter therapy on depression, quality of life, resilience and immune responses in breast cancer survivors]. [Article in Korean] J Korean Acad Nurs. 2011 Jun;41(3):285–-93.
46. Rohan TE, Jain MG, Howe GR, Miller AB. Dietary folate consumption and breast cancer risk. J Natl Cancer Inst. 2000;92(3):266–9.
47. Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenoausal women. Epidemiology. 2001;12(4):420–8.
48. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA. 1999;281(17):1632–7.
49. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA. 1999;281(17):1632–7.
50. Cade JE, Burley VJ, Greenwood DC. Dietary fibre and risk of breast cancer in the UK Women’s Cohort Study. Int J Epidemiol. 2007;36(2):431-438.
51. Mattisson I, Wirfalt E, Johansson U, Gullberg B, Olsson H, Berglund G. Intakes of plant foods, fibre and fat and risk of breast cancer--a prospective study in the Malmo Diet and Cancer cohort. Br J Cancer. 2004;90(1):122–7.
52. Park Y, Brinton LA, Subar AF, Hollenbeck A, Schatzkin A. Dietary fiber intake and risk of breast cancer in postmenopausal women: the National Institutes of Health-AARP Diet and Health Study. Am J Clin Nutr. 2009;90(3):664–1.
53. Dong JY, He K, Wang P, Qin LQ. Dietary fiber intake and risk of breast cancer: a meta-analysis of prospective cohort studies. Am J Clin Nutr. 2011;94(3):900–5.
54. Rock CL, Flatt SW, Thomson CA, et al. Effects of a high-fiber, low-fat diet intervention on serum concentrations of reproductive steroid hormones in women with a history of breast cancer. J Clin Oncol. 2004;22(12):2379–87.
55. Kasim-Karakas SE, Almario RU, Gregory L, Todd H, Wong R, Lasley BL. Effects of prune consumption on the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone. Am J Clin Nutr. 2002;76(6)