Levels of lymphocyte subsets in peripheral blood prior treatment are associated with aggressive breast cancer phenotypes or subtypes

Med Oncol. 2014 Jun;31(6):981. doi: 10.1007/s12032-014-0981-9. Epub 2014 May 6.

Abstract

The aim of this study was to assess associations between ER, Ki67, Her-2 phenotypes, molecular subtypes of breast cancer and circulating levels of lymphocyte subsets (CD4+, CD8+, NK, CD19+, CD20+) and the ratio of CD4+ to CD8+ prior to treatment. Cells from peripheral blood were counted by flow cytometry, ER, Her-2, and Ki67 expressions were detected by pathological examination, and Her-2 was also detected by FISH. We conducted a case-case comparison of 494 women with newly diagnosed breast cancer to evaluate association between levels of lymphocyte subsets in peripheral blood and breast cancer phenotypes [ER- vs. ER+; Ki67 ≥ 14 % vs. Ki67 < 14 %; Her-2+ vs. Her-2-; triple-negative breast cancer (TNBC) vs. luminal A]. Women with the highest levels of CD3+ (OR 0.45, 95 % CI 0.22-0.94), CD4+ (OR 0.22, 95 % CI 0.08-0.59), and the ratio of CD4+/CD8+ (OR 0.17, 95 % CI 0.06-0.47) were least likely to have TNBCs compared with luminal A cancers. The highest tertile of CD8+ (OR 3.67, 95 % CI 1.06-12.72) and NK (OR 2.64, 95 % CI 1.12-6.24) was significantly associated with TNBC compared with luminal A cancer. ER-, Ki67 ≥ 14 %, Her-2+ were associated with low levels of CD4+ and CD4+/CD8+ compared with ER+, Ki67 < 14 %, Her-2-. Women in the highest level of CD8+ had more likelihood to have ER- and Her-2+ compared with ER+ and Her-2-. High levels of NK cells were associated with increased risk of ER- compared with ER+ cancers. Highest levels of CD19+ and CD20+ were associated with low risk of ER-, compared with ER+ cancers. These findings show that immune function differs among different breast cancer phenotypes or subtypes and is associated with ER-, Her-2+, Ki67 ≥ 14 %, and TNBC which are likely to be aggressive phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD19 / metabolism
  • Antigens, CD20 / metabolism
  • Breast Neoplasms / blood*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Killer Cells, Natural / metabolism
  • Lymphocyte Subsets* / metabolism
  • Lymphocyte Subsets* / pathology
  • Middle Aged
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antigens, CD19
  • Antigens, CD20
  • CD3 Complex
  • Ki-67 Antigen
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2