Lentinula edodes mycelia extract plus adjuvant chemotherapy for breast cancer patients: Results of a randomized study on host quality of life and immune function improvement

Nagashima,Yukiko; Yoshino,Shigehumi; Yamamoto,Shigeru; Maeda,Noriko; Azumi,Tatsuya; Komoike,Yoshifumi; Okuno,Kiyotaka; Iwasa,Tsutomu; Tsurutani,Junji; Nakagawa,Kazuhiko; Masaaki,Oka; Hiroaki,Nagano

doi:10.3892/mco.2017.1346

Lentinula edodes mycelia extract plus adjuvant chemotherapy for breast cancer patients: Results of a randomized study on host quality of life and immune function improvement

Authors:
- Yukiko Nagashima
- Shigehumi Yoshino
- Shigeru Yamamoto
- Noriko Maeda
- Tatsuya Azumi
- Yoshifumi Komoike
- Kiyotaka Okuno
- Tsutomu Iwasa
- Junji Tsurutani
- Kazuhiko Nakagawa
- Oka Masaaki
- Nagano Hiroaki
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Affiliations: Department of Breast and Thyroid Surgery, Japan Community Health Care Organization (JCHO) Shimonoseki Medical Center, Shimonoseki, Yamaguchi 750‑0061, Japan, Oncology Center, Yamaguchi University Hospital, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑0046, Japan, Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑0046, Japan, Department of Surgery, Kindai University School of Medicine, Osakasayama, Osaka 589‑8511, Japan, Department of Medical Oncology, Kindai University School of Medicine, Osakasayama, Osaka 589‑8511, Japan, Yamaguchi University, Yamaguchi, Yamaguchi 753‑8511, Japan
Published online on: July 25, 2017 https://doi.org/10.3892/mco.2017.1346
Pages: 359-366
Copyright: © Nagashima et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Anthracycline-based chemotherapies for breast cancer are known to adversely affect patients' quality of life (QOL) and immune function. For that reason, adjuvants that improve those impairments are required. A randomized double‑blind study was conducted to evaluate the effectiveness of Lentinula edodes mycelia extract (LEM), which is an oral biological response modifier (BRM) medicine for cancer patients as such an adjuvant. A total of 47 breast cancer patients who were scheduled to receive postoperative adjuvant anthracycline‑based chemotherapy, i.e., 5‑fluorouracil (5‑FU) + cyclophosphamide + epirubicin (FEC regimen), 5‑FU + cyclophosphamide + doxorubicin/pirarubicin (FAC regimen), cyclophosphamide + doxorubicin/pirarubicin (AC regimen) and cyclophosphamide + epirubicin (EC regimen), were entered in the study. The patients were randomly divided into either an LEM or a placebo tablet group; the tablets were orally ingested daily over 2 courses of each therapy. In the placebo group, the total scores for QOL were lower on day 8 of the second course of chemotherapy compared with the baseline scores, whereas in the LEM group the scores had not decreased. In the placebo group, the QOL functional well‑being score was lower on day 8 after both the first and second courses of chemotherapy compared with the baseline score, but it had not decreased in the LEM group. Evaluation of immunological parameters indicated that an increase in the proportion of regulatory T cells to peripheral blood CD4+ cells tended to be inhibited in the LEM group compared with the placebo group. Oral LEM that was coadministered with anthracycline‑based chemotherapies was useful for maintaining patients' QOL and immune function. Thus, LEM appears to be a useful oral adjuvant for patients receiving anthracycline‑based chemotherapy.

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1	Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet. 365:1687–1717. 2005. View Article : Google Scholar
2	French Adjuvant Study Group: Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 19:602–611. 2001. View Article : Google Scholar : PubMed/NCBI
3	Turner N, Biganzoli L and Di Leo A: Continued value of adjuvant anthracyclines as treatment for early breast cancer. Lancet Oncol. 16:e362–e369. 2015. View Article : Google Scholar : PubMed/NCBI
4	Riccardi A, Brugnatelli S, Giordano M, Danova M, Pugliese P, Tinelli C, Klersy C, Richetti A, Fava S, Nastasi G, et al: Myeloprotective effect of early primary granulocyte-colony stimulating factor during six courses of intensified 5-fluorouracil, epirubicin and cyclophosphamide (120FEC) chemotherapy for advanced breast cancer. Cooperative group of study and treatment of breast cancer. Tumori. 84:540–546. 1998.PubMed/NCBI
5	Baltali E, Günel N, Onat DA, Atahan IL, Akçali Z, Büyukünal E and Firat D: Neoadjuvant chemotherapy in locally advanced breast cancer: A preliminary report. Turkish oncology study group. Tumori. 85:483–487. 1999.PubMed/NCBI
6	Takeuchi H, Saeki T, Aiba K, Tamura K, Aogi K, Eguchi K, Okita K, Kagami Y, Tanaka R, Nakagawa K, et al: Japanese society of clinical oncology clinical practice guidelines 2010 for antiemesis in oncology: Executive summary. Int J Clin Oncol. 21:1–12. 2016. View Article : Google Scholar : PubMed/NCBI
7	Ohzawa H, Miki A, Hozumi Y, Miyazaki C, Sagara Y, Tanaka Y, Shiba S, Joutoku H, Sakuragi M, Takehara M, et al: Comparison between the antiemetic effects of palonosetron and granisetron in breast cancer patients treated with anthracycline-based regimens. Oncol Lett. 9:119–124. 2015.PubMed/NCBI
8	Rapoport BL, Jordan K, Boice JA, Taylor A, Brown C, Hardwick JS, Carides A, Webb T and Schmoll HJ: Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: A randomized, double-blind study. Support Care Cancer. 18:423–431. 2010. View Article : Google Scholar : PubMed/NCBI
9	Berger AM, Lockhart K and Agrawal S: Variability of patterns of fatigue and quality of life over time based on different breast cancer adjuvant chemotherapy regimens. Oncol Nurs Forum. 36:563–570. 2009. View Article : Google Scholar : PubMed/NCBI
10	Kornblith AB, Lan L, Archer L, Partridge A, Kimmick G, Hudis C, Winer E, Casey R, Bennett S, Cohen HJ and Muss HB: Quality of life of older patients with early-stage breast cancer receiving adjuvant chemotherapy: A companion study to cancer and leukemia group B 49907. J Clin Oncol. 29:1022–1028. 2011. View Article : Google Scholar : PubMed/NCBI
11	Martín M, Lluch A, Seguí MA, Ruiz A, Ramos M, Adrover E, Rodriguez-Lescure A, Grosse R, Calvo L, Fernandez-Chacón C, et al: Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): Impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol. 17:1205–1212. 2006. View Article : Google Scholar : PubMed/NCBI
12	Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, et al: Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 13:1050–1059. 2007. View Article : Google Scholar : PubMed/NCBI
13	Mozaffari F, Lindemalm C, Choudhury A, Granstam-Björneklett H, Helander I, Lekander M, Mikaelsson E, Nilsson B, Ojutkangas ML, Osterborg A, et al: NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy. Br J Cancer. 97:105–111. 2007. View Article : Google Scholar : PubMed/NCBI
14	Kawanishi T, Ikeda-Dantsuji Y and Nagayama A: Effects of two basidiomycete species on interleukin 1 and interleukin 2 production by macrophage and T cell lines. Immunobiology. 215:516–520. 2010. View Article : Google Scholar : PubMed/NCBI
15	Sugano N, Hibino Y, Choji Y and Maeda H: Anticarcinogenic actions of water-soluble and alcohol-insoluble fractions from culture medium of Lentinus edodes mycelia. Cancer Lett. 17:109–114. 1982. View Article : Google Scholar : PubMed/NCBI
16	Sugano N, Choji Y, Hibino Y, Yasumura S and Maeda H: Anticarcinogenic action of an alcohol-insoluble fraction (LAP1) from culture medium of Lentinus edodes mycelia. Cancer Lett. 27:1–6. 1985. View Article : Google Scholar : PubMed/NCBI
17	Liu M, Li J, Kong F, Lin J and Gao Y: Induction of immunomodulating cytokines by a new polysaccharide-peptide complex from culture mycelia of Lentinus edodes. Immunopharmacology. 40:187–198. 1998. View Article : Google Scholar : PubMed/NCBI
18	Tanaka K, Matsui Y, Ishikawa S, Kawanishi T and Harada M: Oral ingestion of Lentinula edodes mycelia extract can restore the antitumor T cell response of mice inoculated with colon-26 cells into the subserosal space of the cecum. Oncol Rep. 27:325–332. 2012.PubMed/NCBI
19	Tanaka K, Ishikawa S, Matsui Y, Tamesada M, Harashima N and Harada M: Oral ingestion of Lentinula edodes mycelia extract inhibits B16 melanoma growth via mitigation of regulatory T cell-mediated immunosuppression. Cancer Sci. 102:516–521. 2011. View Article : Google Scholar : PubMed/NCBI
20	Yamaguchi Y, Miyahara E and Hihara J: Efficacy and safety of orally administered Lentinula edodes mycelia extract for patients undergoing cancer chemotherapy: A pilot study. Am J Chin Med. 39:451–459. 2011. View Article : Google Scholar : PubMed/NCBI
21	Okuno K and Uno K: Efficacy of orally administered Lentinula edodes mycelia extract for advanced gastrointestinal cancer patients undergoing cancer chemotherapy: A pilot study. Asian Pac J Cancer Prev. 12:1671–1674. 2011.PubMed/NCBI
22	Suzuki N, Takimoto Y, Suzuki R, Arai T, Uebaba K, Nakai M, Strong JM and Tokuda H: Efficacy of oral administration of Lentinula edodes mycelia extract for breast cancer patients undergoing postoperative hormone therapy. Asian Pac J Cancer Prev. 14:3469–3472. 2013. View Article : Google Scholar : PubMed/NCBI
23	Nagashima Y, Maeda N, Yamamoto S, Yoshino S and Oka M: Evaluation of host quality of life and immune function in breast cancer patients treated with combination of adjuvant chemotherapy and oral administration of Lentinula edodes mycelia extract. Onco Targets Ther. 6:853–859. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kurihara M, Shimizu H, Tsuboi K, Kobayashi K, Murakami M, Eguchi K and Shimozuma K: Development of quality of life questionnaire in Japan: Quality of life assessment of cancer patients receiving chemotherapy. Psychooncology. 8:355–363. 1999. View Article : Google Scholar : PubMed/NCBI
25	Bacik J, Mazumdar M, Murphy BA, Fairclough DL, Eremenco S, Mariani T, Motzer RJ and Cella D: The functional assessment of cancer therapy-BRM (FACT-BRM): A new tool for the assessment of quality of life in patients treated with biologic response modifiers. Qual Life Res. 13:137–154. 2004. View Article : Google Scholar : PubMed/NCBI
26	Schmidt ME, Wiskemann J, Armbrust P, Schneeweiss A, Ulrich CM and Steindorf K: Effects of resistance exercise on fatigue and quality of life in breast cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial. Int J Cancer. 137:471–480. 2015. View Article : Google Scholar : PubMed/NCBI
27	Mozaffari F, Lindemalm C, Choudhury A, Granstam-Björneklett H, Lekander M, Nilsson B, Ojutkangas ML, Osterborg A, Bergkvist L and Mellstedt H: Systemic immune effects of adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide and/or radiotherapy in breast cancer: A longitudinal study. Cancer Immunol Immunother. 58:111–120. 2009. View Article : Google Scholar : PubMed/NCBI
28	Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al: Intraepithelial CD8⁺ tumor-infiltrating lymphocytes and a high CD8⁺/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 102:18538–18543. 2005. View Article : Google Scholar : PubMed/NCBI
29	Yamaguchi T and Sakaguchi S: Regulatory T cells in immune surveillance and treatment of cancer. Semin Cancer Biol. 16:115–123. 2006. View Article : Google Scholar : PubMed/NCBI
30	Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, et al: Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 10:942–949. 2004. View Article : Google Scholar : PubMed/NCBI
31	Tanigawa K, Ito Y, Sakai M and Kobayashi Y: Evaluation of quality of life and immune function in cancer patients receiving combined immunotherapy and oral administration of lentinula edodes mycelia extract. Gan To Kagaku Ryoho. 39:1779–1781. 2012.(In Japanese). PubMed/NCBI
32	Maeda K, Hazama S, Tokuno K, Kan S, Maeda Y, Watanabe Y, Kamei R, Shindo Y, Maeda N, Yoshimura K, et al: Impact of chemotherapy for colorectal cancer on regulatory T-cells and tumor immunity. Anticancer Res. 31:4569–4574. 2011.PubMed/NCBI
33	Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL and Banham AH: Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 24:5373–5380. 2006. View Article : Google Scholar : PubMed/NCBI
34	Ercolini AM, Ladle BH, Manning EA, Pfannenstiel LW, Armstrong TD, Machiels JP, Bieler JG, Emens LA, Reilly RT and Jaffee EM: Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response. J Exp Med. 201:1591–1602. 2005. View Article : Google Scholar : PubMed/NCBI
35	Liu S, Foulkes WD, Leung S, Gao D, Lau S, Kos Z and Nielsen TO: Prognostic significance of FOXP3+ tumor-infiltrating lymphocytes in breast cancer depends on estrogen receptor and human epidermal growth factor receptor-2 expression status and concurrent cytotoxic T-cell infiltration. Breast Cancer Res. 16:4322014. View Article : Google Scholar : PubMed/NCBI
36	Aruga T, Suzuki E, Saji S, Horiguchi S, Horiguchi K, Sekine S, Kitagawa D, Funata N, Toi M, Sugihara K and Kuroi K: A low number of tumor-infiltrating FOXP3-positive cells during primary systemic chemotherapy correlates with favorable anti-tumor response in patients with breast cancer. Oncol Rep. 22:273–278. 2009.PubMed/NCBI
37	Rech AJ, Mick R, Kaplan DE, Chang KM, Domchek SM and Vonderheide RH: Homeostasis of peripheral FoxP3(+) CD4 (+) regulatory T cells in patients with early and late stage breast cancer. Cancer Immunol Immunother. 59:599–607. 2010. View Article : Google Scholar : PubMed/NCBI