title: 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 mm2for 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.
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, Minnesota. degnim.amy@mayo.edu.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Degnim
authors.affiliation: Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Hoskin
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Arshad
authors.affiliation: Women's Cancer Program, Mayo Clinic, Rochester, Minnesota.
authors.forename: Marlene H
authors.initials: MH
authors.lastname: Frost
authors.affiliation: Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Winham
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rushin A
authors.initials: RA
authors.lastname: Brahmbhatt
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pena
authors.affiliation: Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jodi M
authors.initials: JM
authors.lastname: Carter
authors.affiliation: Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Melody L
authors.initials: ML
authors.lastname: Stallings-Mann
authors.affiliation: Women's Cancer Program, Mayo Clinic, Rochester, Minnesota.|Medical Oncology Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Murphy
authors.affiliation: Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Miller
authors.affiliation: Information Technology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Denison
authors.affiliation: Epidemiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Celine M
authors.initials: CM
authors.lastname: Vachon
authors.affiliation: Immunology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
authors.affiliation: Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Radisky
authors.affiliation: Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
mesh_terms: D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001940:Breast / Q000276:immunology / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology
chemical_list: D018951:Antigens, CD20