Cytotoxic T cell depletion with increasing epithelial abnormality in women with benign breast disease

Sabina Adhikary, Tanya L. Hoskin, Melody L. Stallings-Mann, Muhammad Arshad, Marlene H. Frost, Stacey J. Winham, Alvaro Peña, Delphine J. Lee, Linda M. Murphy, Michele Rakoff, Lori A. Denison, Keith L. Knutson, Derek C. Radisky, Daniel W. Visscher, Amy C. Degnim

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Purpose: We quantified cytotoxic T cells in nonmalignant breast tissues from women with and without subsequent breast cancer to assess evidence of whether immunosurveillance may be suppressed prior to tumor development. Methods: We used an age-matched set of breast tissues from women with benign breast disease (BBD) who subsequently developed breast cancer (BBD with later BC), women with BBD who remained cancer free (BBD cancer-free), and normal Komen Tissue Bank (KTB) tissue donors (KTB controls). We evaluated terminal duct lobular units (lobules) for degree of epithelial abnormality and density of dual-positive CD8/CD103 T cells, as CD103+ cells are thought to be a subset of CD8+ cytotoxic T cells located primarily in the intraepithelial compartment. Results: In 10 sets of age-matched women, 256 breast lobules were studied: 85 in BBD women with later BC, 85 in BBD cancer-free women, and 86 in KTB donors. The majority of all lobules were histologically normal (N = 143, 56%), with 65 (25%) nonproliferative fibrocystic change, and 48 (19%) proliferative epithelial change (with or without atypia). In BBD women with later BC, median CD8+/CD103+ cell density was 39.6, 31.7, and 10.5 cells/mm2 (p = 0.002) for normal, nonproliferative, and proliferative lobules. In BBD cancer-free women, median CD8+/CD103+ cell density values were 46.7, 14.3, and 0 cells/mm2 (p = 0.004) respectively. In KTB donors, CD8+/CD103+ cell density was not significantly different across the lobule types (medians 0, 5.8, 10.7, p = 0.43). Conclusion: In women with BBD, breast lobules with increasing epithelial abnormality show significant decreases in cytotoxic T cells as measured by CD8/CD103 staining, suggesting that impaired immunosurveillance may be a component of the earliest stages of breast cancer development.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalBreast Cancer Research and Treatment
Volume180
Issue number1
DOIs
StatePublished - Feb 1 2020

Keywords

  • Benign breast disease
  • Breast cancer
  • Cancer risk
  • Cytotoxic T cells
  • Immunosurveillance
  • Intraepithelial lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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