Inflammatory Breast Cancer (IBC) is an aggressive and unique form of breast cancer that develops rapidly. IBC, like non-IBC breast cancers, is a heterogeneous disease and can occur as any of the six molecular breast cancer subtypes. However, they are most commonly either triple negative; that is presenting with an absence of estrogen receptor (ER-), progesterone receptor (PR-) and the epidermal growth factor receptor 2 (HER2-) or ER-, PR- and HER2+ overexpressed. There is no specific IBC treatment; thus, it seems possible to find a therapeutic for this deadly disease. Our published data demonstrates that Ganoderma lucidum (Reishi) inhibits the viability of the triple negative IBC SUM149 cell line, but not of MCF10A noncancerous mammary epithelial cells. Subsequently, in this study, we aimed to investigate Reishi effects in the viability and molecular signaling of the ER-, PR-, HER2+ IBC cell lines SUM190, KPL-4 and IBC-3. Furthermore, we studied the effects of Reishi on IBC cells when treated in complement with the HER2 Tyrosine Kinase Inhibitor, lapatinib. The hypothesis for this study is that Reishi inhibits cancer cell viability and sensitizes IBC cells to lapatinib therapy and downregulates key proteins overexpressed in IBC. Herein, SUM190, KPL-4 and IBC-3 cells were treated with increasing concentrations of lapatinib and/or Reishi for 24 or 72h. The combination of lapatinib plus Reishi reduced cell viability of KPL-4 cells to 80% when treated with a concentration of 0.25 mg/mL of Reishi for 72h. Additionally, our data shows a reduction in cell viability of 70% in SUM190 cells treated with lapatinib plus Reishi for 72h. Also, Reishi and lapatinib downregulate the expression HER2 in KPL-4 cell after 72h of treatment. Our results provide evidence that Reishi inhibits cancer cell viability, highlighting the potential of Reishi as a natural anti-IBC-therapeutic. This project was sponsored by NIH/NCI #1F31 CA174307 to ISA, Title V PPOHA US Department of Education #P031M105050 to UCC/LAC, NIH/RCMI #G12 MD007583 to UCC/MMM, NIH/INBRE #5P20 GM103475 to UPR/UCC/MMM, NIH/NIMHD U54 MD008149 UH/MMM.

Citation Format: Yismeilin Feliz-Mosquea, Ivette Suarez-Arroyo, Yaliz Loperena, Luis A. Cubano, Michelle M. Martinez-Montemayor. Enhancing response of Ganoderma lucidum (Reishi) and lapatinib in HER2+ inflammatory breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5556. doi:10.1158/1538-7445.AM2015-5556