Naturopathic Approaches to Breast Health

1. Naturopathic Approaches to Breast Health

2. Diet A low glycemic diet appears to be protective against breast cancer. Lajous M, Willett W, Lazcano-Ponce E, et al: Glycemic load, glycemic index, and the risk of breast cancer among Mexican women.  Cancer Causes Control  2005; 16:1165-1169. Dumitrescu RG, Cotarla I: Understanding breast cancer risk where do we stand in 2005?.  J Cell Mol Med  2005; 9:208-221.

3. Diet In general, following an anti-inflammatory, Mediterranean-style diet based on whole foods which are low in saturated fat from animal sources and high in fiber, emphasizing foods such as fruits, berries, vegetables, beans, legumes, and whole grains is advised. Some patients benefit from gluten or dairy-free diets.

4. The Brassica Family Vegetables Brassica vegetables: broccoli, cauliflower, Brussels sprouts, and cabbage. Contain indole-3-carbinols (I3C) and di-indole methane (DIM) which have been shown to increase the ratio of 2-hydroxyestrones to 16-hydroxyestrones. These compounds have also been shown to induce apoptosis, regulate estrogen receptor response, and inhibit proliferation. I3C 400 mg/day has been shown to be well tolerated and has the same favorable effect on 2-OHE/16-OHE ratio. Reed GA, et al: A phase I study of indole-3-carbinol in women: Tolerability and effects.  Cancer Epidemiol Biomarkers Prev  2005; 14:1953-1960.

5. Polyunsaturated fatty acids(PUFAs) A diet where the ratio of ω-3 and ω-6 FAs approximates 1:1-1:4 versus the more commonly seen 1:10- 1:30 of the SAD appears to be protective against breast cancer and a broad spectrum of other disorders including CVD, affective disorders, inflammatory conditions and other cancers. Emily Sonestedt, et al. Do both heterocyclic amines and Omega-6 PUFAs contribute to the incidence of breast cancer in postmenopausal women of the Malmö diet and cancer cohort? Internat J Cancer123 (7): 1637–1643,2008.

7. TX, PG, PG1 LK Inflammatory +/-

8. Omega-3 FA Omega-3: (EPA/DHA) are anti-inflammatory, modulate estrogen metabolism and receptor response. They have also been shown to be cytotoxic. Terry PD, et al Intakes of fish and marine fatty acids and the risks of cancer of the breast and prostate and of other hormone-related cancers: A review of the epidemiologic evidence.  Am J Clin Nutr  2003; 77:532-543. Menendez JA, et al: Effect of gamma-linolenic acid on transcriptional activity of the Her-2/neu (erbB-2) oncogene.  J Natl Cancer Inst  2005; 97:1611-1615.

9. GLA A preliminary study found that GLA, a ω-6 fatty acid, substantially decreased levels of HER-2/neu protein and inhibited its activity in breast cancer cell lines. Concurrent treatment of the cell lines with anti–HER-2/neu trastuzumab (Herceptin) led to a synergistic increase in cytotoxicity and decreased growth. Though GLA is an ω-6 FA, it has anti-inflammatory effects. Sources of GLA: Evening Primrose Oil (Oenothera biennis) and Black Current Oil (Ribes nigrum)

10. To date, there is some evidence supporting GLA as a treatment for mastalgia. Olsson, ME et al, Inhibition of cancer cell proliferation in vitro by fruit and berry extracts and correlations with anti-oxidant levels. J Agric Food Chem. 2004;52:7264-7271.

11. Omega-9/ Oleic acid Oleic acid has been found to suppress HER-2/neu in breast cancer cell lines and also interacts synergistically with trastuzumab by promoting apoptotic cell death in HER-2/neu–positive breast cancer cells Menendez JA,et al: Oleic acid, the main monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2) expression and synergistically enhances the growth inhibitory effects of trastuzumab (Herceptin) in breast cancer cells with Her-2/neu oncogene amplification.  Ann Oncol  2005; 16:359-371.

12. Phytoestrogens • Phytoestrogens are polyphenols originating from plant sources. They are structurally similar to human estradiol and often behave as Selective Estrogen Receptor Modulators (SERMs). These compounds are present in fruits, vegetables, and whole grains. The three main classes are: • Isoflavones: found in legumes, mainly soy • Coumestans: found in clover, alfalfa, and soybean sprouts • Lignans: found in flaxseed.

13. Phytoestrogens Soy and Red Clover (Trifolium praetense) have some estrogenic activity of uncertain clinical significance for ER+ breast cancers. (Beck et alJ Steroid Biochem Mol ,2004, 84(2-3) 259-68.) Trifolium has been shown to more rapidly decrease the number of hot flushes in women as compared to placebo, but after the 12 week trial period, there were no significant differences between trifolium and placebo. Trifolium may interact with anti-coagulants/anti-platelet agents. Tice J, et al. JAMA 2003 Jul 9;290(2):207-14.

14. Soy Isoflavones: A Review of some Pertinent Studies A case controlled study was conducted with 500 women of diverse ethnic background diagnosed with endometrial cancer. 470 ethnically-matched women served as controls. Results indicated that phytoestrogen intake (mainly from soy foods) was inversely related to risk of endometrial cancer, where non-obese postmenopausal women derived the greatest benefit. Horn-Ross PL, et al. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 2003 Aug 6;95(15):1158-64.

15. Soy (90 mg/d isoflavones) was studied in a prospective, randomized, double-blind evaluation of 157 post-menopausal breast cancer patients experiencing hot flashes (4 months post treatment) Primary outcome was number of hot flashes as recorded by patients in a daily menopause diary. Both the active and placebo group demonstrated a reduction in number of hot flashes per day, 54% and 58% respectively. Adverse events included abdominal bloating and flatulence. The authors suggest that soy milk delivering 90 mg per day isoflavones is no more effective than placebo for the management of hot flashes experienced by post-menopausal breast cancer patients.

16. Van Patten CL, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Onco 2002;20:1449-55. Tamoxifen: Animal studies suggest that genistein, a soy isoflavone, may antagonize the effects of tamoxifen on estrogen-dependent breast cancer.

17. The Soy Controversy Soy (Glycine max) may produce estrogenic or anti-estrogenic effects, depending on amounts ingested and levels of circulating estrogens. Reports have appeared concerning the ability of genistein to inhibit the growth of cell lines and transplanted tumors. Overall, the results of studies on soy products and protective associations have been mixed, but there is no good evidence of harm-- either as a preventive measure or affecting the survival of breast cancer patients.

18. In studies of menopausal women and hot flashes, again, the results for soy are mixed, suggesting no significant superiority in relieving menopausal symptoms. The other health advantages of soy products in osteoporosis, in cardiovascular disease, hyperlipidemia and GI health indicate that the use of soy products have utility. Branca F, Lorenzetti S: Health effects of phytoestrogens. Forum Nutr  2005; 57:100-111. Low Dog T, Micozzi M: Women's Health in Complementary and Integrative Medicine: A Clinical Guide, Philadelphia: Elsevier; 2005.

19. Flax/Linum usitatissimum Flaxseed is a rich dietary source of plant lignans and α-linolenic acid (ω-3), and exert anti-estrogenic effects by binding to the Estrogen Receptor and inhibiting the synthesis of estrogen. It is metabolized into enterolactone and enterodiol—structurally similar to estradiol—which may provide the basis for its beneficial effects on estrogen metabolism. In addition, it increases the fecal excretion of conjugated estrogens. Clemons M, Goss P: Estrogen and the risk of breast cancer.  N Engl J Med  2001; 344:276-285.

20. Actions of Flaxseed • Lignans have been shown to stimulate SHBG production in the liver, and inhibit aromatase enzyme activity in pre-adipose cells. • Flaxseed increases urinary excretion of certain estrogen metabolites, particularly 2-OH-estrogen • There is evidence that flaxseed may also reduce insulin-like growth factor I (IGF-I) plasma level concentrations

21. Mousavi Y, Adlercreutz H. Enterolactone and estradiol inhibit each other's proliferative effect on MCF-7 breast cancer cells in culture. J Steroid Biochem Mol Biol ,1992; 41:625-9. Wang C, Makela T, Hase T, et al. Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes. J Steroid Biochem Mol Biol ,1994; 50:205-12. Adlercreutz H, Fotsis T, Bannwart C, et al. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J Steroid Biochem ,1986; 25:791-7.

22. 38 menopausal patients with hypercholesterolemia were randomized to add 38 grams/day of flaxseed or sunflower seed baked into bread or muffin for 6 weeks. After a two week washout period, treatment was resumed for 6 weeks. The flaxseed protocol significantly lowered LDL (14.7%, P<0.001) compared to baseline. Arjmandi, B, et al, Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein-a concentrations in postmenopausal women. Nutr Research, 1998;18:1203-1214.

23. The Inhibition of mammary tumor growth by enterolactone and enterodiol has been reported in vitro. Enterolactone and estradiol are reciprocal inhibitors on the other's proliferative effect on estrogen-dependent breast cancer cells. Rose DP. Dietary fiber and breast cancer. Nutr Cancer 1990; 13:1-8 Serraino M, Thompson LU. The effect of flaxseed supplementation on the initiation and promotional stages of mammary tumorigenesis. Nutr Cancer, 1992:17: 153-9.

24. Animal models indicate that dietary flaxseed inhibits breast cancer cell proliferation and metastasis in both ER+ and ER-models but has no detectable effect on tumor recurrence. Chen J, Wang L, Thompson LU. Flaxseed and its components reduce metastasis after surgical excision of solid human breast tumor in nude mice. Cancer Lett, 2006; 234: 168-75

25. Dietary flaxseed seems to have additive effects when in combination with tamoxifen in inducing tumor regression in estrogen receptor positive breast cancer models Animal models also indicate flaxseed can inhibit the proliferative effect of soy protein on some breast cancer cell lines. Saarinen NM, Power K, Chen J, Thompson LU. Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF-7 human breast cancer xenografts. Int J Cancer 2006: 119:925-31

26. Flaxseed has been shown to inhibit aromatase activity, and thereby enhance metabolism of estrogens to the weak 2-OHEs. It reduces estrogen levels also by retaining it in the gut for elimination in the feces. Various preparations of flaxseed have been used in studies that range from 10 gm/day (2 tbsp/day) of ground flaxseed to 25 gm flaxseed. Both of these produced results indicating a reduction in risk for breast cancer and the potential to inhibit breast tumor growth. Thompson LU, Chen JM, Li T, et al: Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer.  Clin Cancer Res  2005; 11:3828-3835.

27. An interesting older study suggested that flax can directly influence hormone metabolism. Healthy pre-menopausal women ingested 40 g/day of flaxseed for 3 menstrual cycles. There were no significant differences in estradiol or estrone levels, but in the luteal phase, the P/E2 levels were significantly higher in the Flax group and this group exhibited a prolonged luteal phase. Phipps. WR et al, Effect of flaxseed ingestion on the menstrual cycle J Clin Endocrinol Metab. 1993; 77:1215-1219.

28. Whole Grains Whole grains are concentrated sources of fiber, antioxidants, trace minerals and phenolic compounds, lignans, and plant stanols and sterols that have been linked to disease prevention. Whole grains also moderate insulin and glucose responses, helping lower the glycemic load. To date, the best evidence linking specific foods to reduced risk of cancer suggests, in general, a diet rich in fruits, vegetables, and whole grains. Gluten sensitive individuals can substitute gluten free grains.

29. Gluten- Free Substitutes

30. Quinoa

31. Amaranth

32. Millet

33. Tea/Camellia sinensis Epidemiological studies indicate that drinking green tea (3-5 cups/day) may reduce the risk of breast cancer and reduce the recurrence of breast cancer. Seely D, Mills EJ, Wu P, et al. The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancer: a systematic review and meta-analysis. Integ Cancer Ther, 2005; 4:144-55.

34. Mushrooms At this time, there is epidemiologic data, but few studies have been conducted on whole mushroom consumption in humans. In general, mushrooms contain polysaccharide constituents which appear to act immunopotentiators. Polysaccharide krestin (PSK), is a constituent of the coriolus mushroom and has been used in Japan for decades as an adjunct to standard chemotherapy. It appears to improve response and survival time in breast cancer patients. Iino Y, et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res 1995; 15:2907-11.

35. Antioxidants Vitamin C: results from studies concerning the association between Vitamin C and breast health, particularly breast cancer prevention are mixed. Recent work indicates that high dose IV Vitamin C may benefit cancer patients in general. Further, Vitamin C has been shown to have positive effects for atherosclerosis, CVD, the immune system (particularly in children) and a host of other beneficial effects. Gandini S, et al. Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of associated micronutrients. EurJCancer. 2000:36; 636-46 Michels KB, et al. Dietary antioxidant vitamins, retinol, and breast cancer incidence in a cohort of Swedish women. EurJCancer. 200191;563-7.

36. β-carotenes β –carotenes have been shown to play a role in preventing breast cancer. Kim MK, Ahn SH, Lee-Kim. Relationship of serum alpha-tocopherol, carotenoids and retinol with the risk of breast cancer. Nutr Res 2001;21:797-809. Zhang S, Hunter DJ, Forman MR, et al. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J NatlCancerInst,1999;91:547-56. Cramer DW, et al. Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women. Int J Cancer94:128-34.

37. Tocopherols Taking Vitamin E seems to be effective in decreasing the symptoms of both PMS and dysmennorrhea. In at least in one study, there was no efficacy for the reduction of hot flashes in breast cancer survivors. London RS,et al, Efficacy of alpha-tocopherol in the treatment of the premenstrual syndrome. J Reprod Med 1887;32:400-4. Ziaei S, et al. A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea. BJOG 2005; 112: 466-9. Barton DL, et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998; 16495-500.

38. Retinoids, Carotenoids and Tocopherols A prospective study in 2002 investigated the associations of concentrations of retinols, carotenes, and tocopherols with risk of breast cancer. Analysis indicated that all were protective, but that carotenoids had the strongest protective ability. This seemed particularly true in high risk women (FHx/Alcohol) Sato R, Helzlsourer KJ, Alberg AJ, et al: Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer.  Cancer Epidemiol Biomarkers Prev  2002; 11:451-457.

39. Anti-Oxidants and Chemotherapy/Radiation therapy

40. The SU.VI.MAX Study The Supplementation en Vitamines et Mine raux Antioxydants (SU.VI.MAX) study, is a RDBPC primary prevention trial, and tested the efficacy of supplementation with a combination of antioxidant vitamins and minerals, at nutritional doses, in reducing the cancer incidence in a general population unselected for risk factors. After 7.5 years, the study found significant reduction in cancer rates for men only. Herchberg, S et al, Antioxidant vitamins and minerals in prevention of cancers: lessons from the SU.VI.MAX study. Br J Nutr. 2006 Aug;96 Suppl 1:S28-30.

41. Selenium Selected randomized-controlled clinical trials of Selenium as a mono-supplement to alleviate adverse effects (edema and infection) in patients undergoing tumor-specific therapy (chemo, radiation or surgery) were examined. The authors concluded the the evidence neither supported nor rejected the use of Se supplementation during the treatment period(s) examined. Dennert, G, Horneber, M, Selenium for alleviating the side effects of chemotherapy, radiotherapy and surgery in cancer patients. Cochrane Database Syst Rev. 2006 Jul 19;3:CD005037

42. Selenium selenite Selenium selenite was tested in a small study for post-treatment control of edema. Patients were given 1000 µg each day for the first week, 300 µg each day for the second and a 100 µg for 3 months. 10 of 12 patients reported positive effects. Micke O., et al. Selenium in the treatment of radiation-associated secondary lymphedema.  Int J Radiat Oncol Biol Phys 56. (1): 40-49.2003.

43. A literature review was undertaken to examine the issue of concommitant use of antioxidants during chemotherapy or radiation therapy. At least 50 randomized or observational studies were reviewed, involving a total of 8,521 patients with 5,081 using β-carotene, Vitamins A, C and E, Se, Cys, B-vitamins, Vitamins D and K and glutathione. The conclusions were “ non-prescription antioxidants and other nutrients do not interfere with therapeutic modalities for cancer. Furthermore, they enhance the killing of therapeutic modalities for cancer, decrease their side effects, and protect normal tissue. In 15 human studies, 3,738 patients who took non-prescription antioxidants and other nutrients actually had increased survival.”

44. Simone, CB, et al Altern Ther Health Med. 2007 Jan-Feb;13(1):22-8 Simone, CB, et al ,Altern Ther Health Med. 2007 Mar-Apr;13(2):40-7

45. Another literature review examined 31 observational and 21 interventional trials. The authors concluded that inconsistencies in design, timing, malignancy status and therapy protocols precluded any definitive conclusions. They noted, however that anitoxidant status (measured as total radical antioxidant parameter) appears to decline during cancer treatment and that adequately powered studies need to be done to address these associations. Ladas, et al, Antioxidants and cancer therapy: a systematic review. J Clin Oncol. 2004 Feb 1;22(3):517-28

46. In a recent communication, RW Moss argued that current concerns about the use of anti-oxidants was unwarranted based on the available studies and pointed out the therapeutic use of amifostine and dexrazoxane as anti-oxidants to control adverse effect was contradictory to the stated reasons for avoiding antioxidant supplementation. Moss, RW, Integr Cancer Ther. 2006 Mar;5(1):63-82.

47. More recently, another literature review was done evaluating 33 randomized and controlled clinical trials (N=2446). Examined were glutathione, melatonin, vitamin A, an antioxidant mixture, N-acetylcysteine, vitamin E, selenium, L-carnitine, Co-Q10 and ellagic acid. 24 (73%) of the studies reported evidence of decreased chemotherapeutic toxicities with no reported decrease in chemotherapeutic efficacy. One study using Vit A reported an increase in toxicity. 5 of the studies (15%) reported the antioxidant group had more full doses of chemotherapy or less-dose reduction than control groups. Block, KI, et al, Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Int J Cancer. 2008 Sep 15;123(6):1227-39.

48. Greenlee et al looked at 22 studies on the use of anti-oxidant supplements during breast cancer treatment and concluded that no definitive statements could be yet made. Tentatively, there were some indications that some adverse effects of therapy might be ameliorated with the use of anti-oxidants and that melatonin might be contraindicated. • Greenlee, H., et al, Use of antioxidant supplements during breast cancer treatment: a comprehensive review. Breast Cancer Res Treat. 2008 Oct 7.

49. Prasad advocated an active nutritional protocol including high doses of dietary anti-oxidants on the basis that such would increase tumor response and improve efficacy. He also advocated a maintenance nutritional protocol, along with other dietary and lifestyle modifications to reduce the risk of recurrence. Prasad, KN, Multiple dietary antioxidants enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity. Integr Cancer Ther. 2004 Dec;3(4):310-22

50. Anti-Inflammatory Herbs