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Natural Therapies for TNBC
Several natural therapeutic agents have shown promise in retarding the growth of TNBC cell lines in vitro and in animals. The following natural therapies provide us with tools to consider in prevention of recurrence strategies:
- Those with the triple-negative breast cancer phenotype have the lowest average vitamin D levels and the highest percentage of patients who are vitamin D deficient.39 Vitamin D given to a mouse model suppressed multiple proteins that are required for survival of triple-negative/basal-like breast cancer cells.40
- A product called BreastDefend that contains medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin) was found to prevent breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer.41
- Melatonin showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis in TNBC-induced mouse model.42
- Silibinin, given orally from the milk thistle plant, significantly suppressed tumor volume in a TNBC mice model.43
- Epigallocatchin-3-gallate (EGCG), from green tea, induces apoptosis and inhibits cell proliferation and migratory behavior of TNBC cells.44
- Curcumin induces apoptosis and inhibits the proliferation of TNBC cells.45
- Ginseng sapogenins are potent inhibitors of MDA-MB-231 human TNBC cell lines.46
- Piperine, an alkaloid from black pepper, inhibits the growth and motility of TNBC and enhances radiotherapy in vitro.47
- Omega-3 polyunsaturated fatty acids have a pronounced inhibitory effect against triple-negative basal breast cancer cell lines in vitro.48
Conclusion
Information about triple-negative breast cancer is lacking in general. It is reassuring, however, that the interest in studying TNBC appears to be high. The most interesting research, to me, is among those studying individualization of treatment based on gene-expression profiling. Until more information is available, I recommend that those with TNBC get an opinion from an oncology facility in a major metropolitan area. I encourage patients to request genetic testing from their oncologist and be open to neoadjuvant chemotherapy and mastectomy if recommended.
Look for an experienced, licensed, naturopathic physician in your area to help during treatment to reduce side effects and negative interactions between drugs and natural therapeutics. Complementary care providers can also offer strategies for prevention of recurrence. These range from specific dietary and fitness recommendations to individualized treatment plans including vitamins, minerals, and botanical medicines found to reduce the risk of recurrence of breast cancer.
To find experts in your area, go to the American Association of Naturopathic Physicians (naturopathic.org) or the Oncology Association of Naturopathic Physicians (oncanp.org). For more information on triple negative breast cancer in general, go to tnbcfoundation.org.
Notes
1. Benign breast conditions: not all lumps are cancer [online article]. American Cancer Society. 2012. http://www.cancer.org/Treatment/UnderstandingYourDiagnosis/ExamsandTestDescriptions/
ForWomenFacingaBreastBiopsy/breast-biopsy-benign-breast-conditions.
2. 100 questions about TNBC [Web page]. TNBC Foundation. http://www.tnbcfoundation.org/100qanda.htm.
3. Desantis C, Ma J, Bryan L, et al. Breast cancer statistics, 2013. CA Cancer J Clin. January/February 2014;64(1):52–62. Epub Oct 1 2013. Accessed at http://onlinelibrary.wiley.com/doi/10.3322/caac.21203/full.
4. Bauer KR, Brown M, Cress RD, et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and Her2-negative invasive breast cancer, the so-called triple-negative phenotype: a population based study from the California Cancer Registry. Cancer. 2007;109:1721–1728.
5. Jiao Q, Wu A, Shao G, et al. The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers. J Thorac Dis. 2014;6(9):f1329–f1335.
6. Yu F, Zhang X, Zhang S, et al. Patterns and risk factors of recurrence in triple-negative breast cancer. Zhonghua Yi Xue Za Zhi. 2014 Jul 22;94(28):2180–2183.
7. Greenup R, Buchaan A, Loizio W, et al. Prevalence of BRCA mutations among women with triple-negative breast cancer (TNBC) in a genetic counseling cohort. Ann Surg Oncol. Aug. 22, 2013.
8. Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol. 2012;23(Suppl 6):vi7–vi12.
9. Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes and survival in the Carolina Breast Cancer Study. JAMA. 2006;295:2492–2502.
10. Sorlie T, Wang Y, Xiao C, et al. Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer; gene expression analyses across three different platforms. BMC Genomics. 2006;7:127.
11. Stark A, Kleer CG, Martin I, et al. African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study. Cancer 2010;116:4926–4932.
12. Jiao et al. Op cit.
13. Ibid.
14. Tervasmaki A, Winquist R, Jukkola-Vuorinen A, et al.Recurrent CYP2C19 allele is associated with triple-negative breast cancer. BMC Cancer. 2014 Dec 2;2:14(1):902
15. Hong CC, Yao S, McCann SE, et al. Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple-negative breast cancers. Breast Cancer Res Treat. June 2013;39(2):477–488.
16. Ma FJ, Liu ZB, Qu L, et al. Impact of type 2 diabetes mellitus on the prognosis of early stage triple-negative breast cancer in People's Republic of China. Onco Target Ther. 2014 Nov 27;7:2147–2154.
17. Vona-Davis L, Rose DP, Hazard H, et al. Triple-negative breast cancer and obesity in a rural Appalachian population. Cancer Epidemiol Biomarkers Prev. 2008;17:3319–3324.
18. Kwan ML, Kushi LH, Weltzien E, et al. Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res 2009;11:R31.
19. Stead LA, Lash TL, Sobieraj JE, et al. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res. 2009;11:R18.
20. Kwan et al. Op cit.
21. Shinde SS, Forman MR, Kuerer HM, et al. Higher parity and shorter breastfeeding duration: association with triple-negative phenotype of breast cancer. Cancer. 2010;116:4933–4943.
22. Dolle JM, Daling JR, White E, et al. Risk factors for triple-negative breast cancer in women under age 45. Cancer Epidemiol Biomarkers Prev 2009; 18: 1157–1166.
23. Ibid.
24. Phipps AL, Chlebowski RT, Prentic R, et al. Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer. J Natl Cancer Inst 2011;103:470–477.
25. Kabat GC, Kim M, Phipps Al, et al. Smoking and alcohol consumption in relation to risk of triple-negative breast cancer in a cohort of postmenopausal women. Cancer Causes Control 2011;22:775–783.
26. Greenup R, Buchanan A, Lorizio W, et al. Prevalence of BRCA mutations among women with triple-negative breast cancer (TNBC) in a genetic counseling cohort. Annals of Surg Oncol. Epub August 22, 2013.
27. Elsamany S, Abdullah S. Triple-negative breast cancer: future prospects in diagnosis and management. Med Oncol. 2014 Feb;31(2):834.
28. Balko JM, Giltnane JM, Shwartz LJ, et al. Profiling of triple-negative breast cancers after neoadjuvant chemotherapy identifies targetable molecular alterations in treatment-refractory residual disease. 2012 San Antonio Breast Cancer Symposium. Abstract S3-6. Presented Dec. 6, 2012.
29. Jiao et al. Op cit.
30. Loibl S, Jackisch C, Gade S, et al. Neoadjuvant chemotherapy in the very young, 35 years of age or younger. 2012 San Antonio Breast Cancer Symposium. Abstract S3-1 Presented Dec. 6, 2012.
31. Budhi Singh Yadav, Suresh C Sharma, Priyanka Chanana, et al. Systemic treatment strategies for triple-negative breast cancer. World J Clin Oncol. 2014 May, 10;5(2):125–133.
32. Medical updates, treatment options and follow-up care for triple-negative breast cancer [online interview]. Living Beyond Breast Cancer. April, 2014. http://www.lbbc.org/Learning-From-Others/Ask-the-Expert/2014-04-Triple-Negative-Breast-Cancer-Medical-Updates. Accessed December 6, 2014.
33. De Melo Gagliato D, Gonzalez-Angulo AM, Lei X, et al. Clinical impact of delaying initiation of adjuvant chemotherapy in patients with breast cancer. J Clin Oncol. Jan. 27, 2014.
34. Wahdan-Alaswad RS, Cochrane DR, Spoelstra ND, et al. Metformin-induced killing of triple-negative breast cancer cells is mediated by reduction in fatty acid synthase via miRNA-193b. Horm Cancer. 2014 Dec;5(6):374–389.
35. Goh W, Sleptsova-Freidrich I, Petrovic N. Use of proton pump inhibitors as adjunct treatment for triple-negative breast cancers. An introductory study. J Pharm Pharm Sci. 2014;17(3):439–446.
36. Zhang X, Smith-Warner SA, Collins LC, et al. Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. J Clin Oncol. 2012 Oct 1;30(28):3468–3477.
37. Maity G, De A, Banerjee S, et al. Aspirin prevents growth and differentiation of breast cancer cells: Lessons from in vitro and in vivo studies. Presented at: Annual meeting of the American Society for Biochemistry and Molecular Biology and Experimental Biology. Boston, MA; April 20–24, 2013. Abstract 606.
38. Gucalp A, Tolaney SM, Isakoff SJ, et al. Targeting the androgen receptor (AR) in women with AR+ ER-/PR- metastatic breast cancer (MBC). Presented at: Annual meeting of the American Society of Clinical Oncology. June 1–5, 2012; Chicago, IL. Abstract 1006.
39. Rainville C, Khan Y, Tisman G. Triple negative breast cancer patients presenting with low serum vitamin D levels: a case series. Cases J. 2009 July 21;2:8390.
40. LaPorta E, Welsh J. Modeling vitamin D actions in triple negative/basal-like breast cancer. J Steroid Biochem Mol Biol. 2014 Oct;144.
41. Jiang J, Thyagarajan-Sahu A, Loganathan J, et al. BreastDefendtm prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer. Oncol Rep. 2012 Oct;28(4):1139–1145.
42. Jardim-Perassi BV, Arbab AS, Ferreira LC, et al. Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer. PLoS One. 2014 Jan 9;9(1):e85311.
43. Kil WH, Kim SM, Lee JE, et al. Anticancer effect of silibinin on the xenograft model using MDA-MB-468 breast cancer cells. Ann Surg Treat Res. 2014 Oct;87(4):167–173.
44. Braicu C, Gherman CD, Irimie A, et al. Epigallocatechin-3-Gallate (EGCG) inhibits cell proliferation and migratory behavior of triple negative breast cancer cells. J Nanosci Nanotechnol. 2013 Jan;13(1):632–637.
45. Sun XD, Liu XE, Huang DS. Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EDGR expression. Mol Med Rep. 2012 Dec 6(6):1267–1270.
46. Kwak JH, Park JY, Lee D, et al. Inhibitory effects of ginseng sapogenins on the proliferation of triple negative breast cancer MDA-MB-231 cells. Bioorg Med Chem Lett. 2014 Oct 22;24(23):5409–5412.
47. Greenshields AL, Couicette CD, Sutton KM, et al. Piperine inhibits the growth and motility of triple-negative breast cancer cells. Cancer Lett. 2014 Nov 13.
48. Pogash TJ, El-Bayoumy K, Amin S, et al. Oxidized derivative of docosahexaenoic acid preferentially inhibit cell proliferation in triple negative over luminal breast cancer cells. In Vitro Cell Dev Biol Anim. Epub 2014 Nov 21.
 Dr. Barbara MacDonald is a licensed naturopathic doctor, acupuncturist, and Chinese herbalist practicing in Camden, Maine. She is the coauthor of The Breast Cancer Companion: A Complementary Care Manual: The Practitioner's Guide to Support Women Through Conventional Cancer Treatment. This article is adapted from a new section of this textbook, 4th edition, to be published later this year. Barbara is a 1997 graduate of National College of Naturopathic Medicine; a member of the American Association of Naturopathic Physicians, the Oncology Association of Naturopathic Physicians, and the Maine Association of Naturopathic Doctors and Acupuncturists; and a charter member of Destination Wellness Midcoast Maine. Dr. MacDonald has a general practice wherein she helps those with chronic illness, cancer, and other health challenges to eliminate obstacles to optimal health and inspires them to fully express their highest and best selves.
Contact: www.camdenwholehealth.com or drbarbmacdonald@yahoo.com; 207-230-1131.
The 4th edition of The Breast Cancer Companion: A Complementary Care Manual: The Practitioner's Guide to Support Women through Conventional Cancer Treatment,will be available soon. This well-referenced text has been edited cover to cover by specialists in the field of conventional and naturopathic oncology. This clinical text provides details on what patients experience from diagnosis through the end of treatment, followed by a new section on prevention of recurrence strategies, as well as up-to-date research on complementary naturopathic therapeutics to limit side effects and promote healing. For advanced notice regarding publication date, e-mail Barbara MacDonald, ND, LAc, at drbarbmacdonald@yahoo.com.
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