Breast cancer (BC) is one of the most common cancers among women worldwide that ~25% of new cancer cases diagnosed every year would be BC; moreover, ~15% of cancer deaths per year caused by BC makes it the leading cause of cancer death among women worldwide. To date, though the cause of a large proportion of BC are still unclear, recent studies have revealed that a supportive breast tissue microenvironment is critical for the development and progression of BC, especially the communication with immune cells within breast tissue. Therefore, breast inflammatory microenvironment is currently received a substantial attention in the prevention and treatment of BC. Research on breast cancer immunology suggests that inflammatory mediators, estrogen and several inflammation-related tumorigenic pathways are potentially contributors for inflammatory breast tumorigenesis. It is evidenced that elevated levels of inflammatory mediators, such as cytokines, chemokines, prostaglandins, and enhanced estrogen production while suffering from chronic inflammation is responsible for not only activating oncogenic pathways, for example NF-κB, STAT3 and Wnt signaling pathways, but also reducing the efficacy of cancer-specific immunity against tumor cells. Accordingly, targeting the chronic inflammatory status in breast tissue has become a promising strategy for breast cancer therapy. Recently, due to the annoying side effects accompanying by traditionally anticancer drugs, there is an increased interest in finding out natural sources to treat BC. Herein, we report that antroquinonol (AQ) and/or 4-acetylantroquinonol B (4-AAQB) isolated from Antrodia Camphorata were able to modulate the expression of several inflammatory mediators, IL-6 and IFN-γ in particular, and downregulate the aromatase expression and Wnt signaling responses induced by inflammatory status. Taken together, the present findings provide new insights into the role of AQ and 4-AAQB in inflammatory breast tumors and also suggest them as promising candidates for breast cancer immunotherapy.