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

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.