Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development

Abstract

Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD).Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm² for CD4⁺ T cells, CD8⁺ T cells, CD20⁺ B cells, and CD68⁺ macrophages and quantification of positive pixel measure for CD11c (dendritic cells).Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8⁺ T cells, CD11c⁺ dendritic cells, CD20⁺ B cells, and CD68⁺ macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20⁺ cell density (P = 0.04). Nearly 42% of BBD cases had no CD20⁺ B cells in evaluated lobules compared with 28% of BBD controls (P = 0.02). The absence of CD20⁺ cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk.Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945-52. ©2017 AACR.