Ganoderma lucidum (Reishi) is a medicinal mushroom used to treat among many diseases, hyperglycemia, inflammation and cancer. Our laboratory studies the effects Reishi, as an alternative approach to treat Inflammatory Breast Cancer (IBC). IBC is an aggressive form of breast cancer. IBC symptoms include a diffuse redness and swelling of the breast, which resembles inflammation and may suggest the involvement of both immunological and inflammatory processes in the pathogenesis of this disease. Pathological findings indicate the presence of tumor emboli invading the dermal lymphatics of the breast. In these tumors pro-inflammatory mediators such as interleukin-8 (IL-8), IL-6, and Monocyte Chemotactic Protein 1 (MCP-1) are produced to contribute to cancer progression. These proteins are regulators of the immune system but in the tumor microenvironment they can act as growth factors, allowing tumor cell survival, invasion and metastasis. Our published data demonstrates that Reishi disintegrates tumor emboli, reduces tumor growth and modulates the abundance of plasma membrane proteins involved in downstream signaling of invasion cascades. Herein, we are characterizing cytokine production in vitro and in vivo and their modulation upon Reishi treatment. SUM-149 conditioned media was analyzed via cytokine bead array to quantify cytokine production after 0 or 0.5mg/mL Reishi treatment at different time points. For in vivo studies, severe combined immunodeficient (SCID) mice were treated daily for two weeks with 0, 7, 14 or 28mg/kg BW of Reishi via oral gavage. At two weeks the mice were injected with SUM-149 IBC cells in their mammary fat pad and continued oral gavage treatment for an additional 14 weeks. Our in vitro study data shows that SUM-149 cells secrete IL-6 and IL-8 and that secretion of these cytokines, which are known to behave as growth factors, was decreased by 23% and 76% respectively after 48 hours of Reishi treatment. As of 10 weeks of the study, tumor size is reduced in all Reishi treated animals when compared with vehicles. Interestingly, Reishi shows a tendency to decrease the expression of MCP-1 and IL-6 in plasma, while a slight increase in TNF-α is observed. Our results show that Reishi has an immunomodulatory role, demonstrated by its ability to reduce cytokine production both in cells and in mice plasma. Reishi may be used as a targeted therapeutic for women afflicted with IBC, for whom no direct therapeutics are currently available. This project was sponsored by Title V PPOHA US Dept of Education #P031M105050 to UCC, NIH/RCMI #2G12RR003035 to UCC, NIH/INBRE #5P20RR016470 to UPR/UCC, NIH/NCRR #U54RR026139 to UPR/UCC, and a research donation from the Commonwealth of Puerto Rico to UCC-Centro Universitario de Medicina Integral y Complementaria (CUMIC) / MMM. Citation Format: Yaliz Loperena-Alvarez, Luis A. Cubano, Michelle M. Martínez-Montemayor. Effects of Ganoderma lucidum on cytokine expression in Inflammatory Breast Cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4727. doi:10.1158/1538-7445.AM2013-4727