title: Levels of lymphocyte subsets in peripheral blood prior treatment are associated with aggressive breast cancer phenotypes or subtypes.
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.
authors.affiliation: Department of General Surgery, XinHua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665. Kong Jiang Road, Shanghai, 200092, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Jia
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhu
authors.forename: Longlong
authors.initials: L
authors.lastname: Ding
authors.forename: Kejin
authors.initials: K
authors.lastname: Wu
authors.forename: Yunshu
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000368:Aged; D018941:Antigens, CD19 / Q000378:metabolism; D018951:Antigens, CD20 / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D017252:CD3 Complex; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human