Predictive and prognostic value of circulating blood lymphocyte subsets in metastatic breast cancer

Abstract

The treatment of breast cancer (BC) has improved greatly in recent years, however, the limitations of current therapeutic modalities underscore the need to define new prognostic tools and develop highly targeted therapies. The aims of the present study were to explore the effects of circulating blood lymphocyte subsets on the survival of metastatic breast cancer (MBC) patients and to evaluate their predictive and prognostic value. The clinical data of 482 patients with MBC were retrospectively analyzed, and patients were grouped according to molecular types of BC. The distribution of peripheral blood lymphocyte subsets at the time of first metastasis was examined by flow cytometry, and the distribution of lymphocyte subsets in each group was categorized into ''high or low'' subgroups using the upper quartile point as the cutoff. The relationship between the distribution of lymphocyte subsets and progression-free survival (PFS) as well as overall survival (OS) was evaluated in diverse molecular MBCs. In multivariate analysis, CD4⁺ was a negative independent predictor of PFS (hazard ratio [HR] = 0.538, 95% confidence interval [CI] = 0.313-0.926, P = 0.025) and CD3⁺ was a poor independent prognostic factor for OS (HR = 0.437, 95% CI = 0.248-0.772, P = 0.004) in the human epidermal growth factor receptor 2 (HER2)-positive group. Neither the CD8⁺ , CD19⁺ , and CD56⁺ lymphocyte subsets nor the CD4⁺ /CD8⁺ ratio in peripheral blood was significant predictive or prognostic factors. In conclusion, higher circulating levels of CD4⁺ and CD3⁺ at first diagnosis in HER2-overexpressing MBC were significantly associated with worse survival outcomes. Low levels of plasma CD4⁺ and CD3⁺ were associated with increased anti-HER2 benefit in HER2-positive MBC. The present results indicate that these factors can be used as predictive and prognostic indicators of the outcome of patients with MBC.

Keywords: CD3; CD4; lymphocytes; metastatic breast cancer; survival.

Figure 1

A‐E, Distribution of peripheral blood CD3⁺, CD8⁺, CD4⁺, CD19⁺, and CD56⁺ in different molecular types of MBC; F, Ratio of CD4⁺ to CD8⁺ in different molecular types of MBC. M is the median of the proportion of each lymphocyte subpopulation

Figure 2

A, Relationship between the distribution of plasma CD3⁺ and PFS in the HER2‐positive group; B, Relationship between the distribution of plasma CD4⁺ and PFS in the HER2‐positive group; C, Relationship between the distribution of plasma CD3⁺ and OS in the HER2‐positive group; D, Relationship between the distribution of plasma CD4⁺ and OS in the HER2‐positive group