Epidemiological studies have consistently shown that increased mammographic density (MD) is a strong risk factor for breast cancer. We previously observed an elevated number of vimentin+/CD45+ leucocytes in high MD (HMD) epithelium. To date, there is little data on the association of MD with immune cell infiltration. In this study, we aimed to further investigate the subtypes of immune cell infiltrates in high and low MD (LMD) breast tissue.
Fifty-four women undergoing prophylactic mastectomy at Peter MacCallum Cancer Centre or St Vincent’s Hospital were enrolled. Upon completion of mastectomy, high and low MD areas were resected under radiological guidance in collaboration with Breast Screen Victoria, and were subsequently fixed, processed and sectioned. Fifteen paired high and low MD specimens were further selected according to their fibro-glandular characteristics (reasonable amount of tissue /per block) on haematoxylin & eosin staining for subsequent immunohistochemical analyses of immune cell infiltration.
Overall, immune cell infiltrates were predominantly present in breast ducts and lobules, rather than in the stroma, with CD68+ macrophages and CD20+ B lymphocytes also surrounding the vasculature. Macrophages, dendritic cells (DCs), B lymphocytes, and programmed cell death protein-1 (PD-1) expression were significantly increased in HMD epithelium compared to LMD. Moreover, a significantly higher level of DCs, CD4+ T cells and PD-1 were also observed in HMD stroma. We are currently assessing the number of T-regulatory cells and also the cytokine milieu in order to define the Th1/Th2 microenvironment.
Although breast cancer is not classically considered to be immunoresponsive, our study suggests a dynamic breast immune microenvironment where HMD tissue is associated with increased immune cell infiltration and enhanced PD-1 expression. This suggests the immune system may be activated very early in breast cancer development and may in part underpin the breast cancer risk associated with HMD.