The role of lymphocytes and macrophages in human breast tumorigenesis: An immunohistochemical and morphometric study

The objective of the present study was to analyze the function of lymphoid elements in the tumorigenesis of human breast cancer, similar to their elucidation in human ovarian cancer in our previous work. The lymphocytic and macrophageal content of lymphocytes and macrophages was analyzed immunohistochemically and morphometrically in 49 human breast tumors of different types. The following types of tumors were studied: 1) fibrocystic disease, 2) fibroadenoma, 3) carcinoma in situ, 4) infiltrating ductal and lobular carcinoma with high lymphoid infiltration, and 5) infiltrating ductal and lobular carcinoma with lymphoid depletion. The first two had little lymphoid infiltration and few lymphocytes (mainly T cells), while carcinoma in situ had extensive lymphoid infiltration and increased lymphocytic density, the consequence of a sharp rise in total lymphocytes reflecting the intensified immune response. In ductal and lobular infiltrating carcinoma with high infiltration, T cells were in large excess of B cells (81% and 87% vs. 11%) and CD8+ lymphocytes were the predominant type of T cells (up to 90%), in both tumoral parenchyma and stroma. In infiltrating carcinoma with lymphoid depletion, the total lymphocyte and macrophage count and areas of lymphoid infiltrates decreased, relative to highly infiltrated carcinomas, as signs of deep subcompensation of the lymphoid system. The host's reaction to disease was reflected in high correlations between the densities of the lymphoid cellular elements as tumorigenesis evolved. We suggest that the stromal immunocompetent cells are a reservoir of T killers that eventually cross into the parenchyma and join T helpers and B lymphocytes in the immune antitumor response. In later stages of cancer the response is exhausted, as manifested in lymphoid subcompensation.