Abstract
ABSTRACT Background Lymphopenia ( 1 Giga/L) before initiation of chemotherapy is a predictive factor for toxicity and death in metastatic phase for cancer patients. Combinatorial diversity of T Cell Receptor -beta chain (TCR-β), as a measure of T cell repertoire diversity, was investigated and tested either alone or in combination with lymphopenia as a prognostic factor for overall survival (OS) in first line treatment of metastatic breast cancer (MBC) patients. Methods Using semi quantitative multiplex PCR, the V-D-J combinatorial diversity of the TCR was measured on cryo-preserved blood samples from 2 cohorts of MBC patients before the initiation of the first line chemotherapy: in an experimental cohort (cohort A, n = 66) and in a validation series (cohort B, n = 67). A prognostic score, defined NDL (Number & Diversity of Lymphocytes) combining lymphocyte count and TCR diversity was delineated. Univariate and multivariate analysis of prognostic factors for OS were performed in both cohorts. Results Lymphopenia ( 1 Giga/L) was associated with shorter OS for cohort B while TCR diversity ≤33% (called divpenia) was associated with a reduced OS in cohort A. The combination of lymphopenia with low TCR diversity (called lympho-divpenia) was associated with poor OS compared to patients with either lymphocyte count ≥1 Giga/L or diversity >33% or both, in cohort A (median OS: 7.6 vs 24.5 months, p.value =0.0006) and cohort B (median OS 10.6 vs 22.9 months, p.value =0.0035). In a multivariate analysis, including all significant clinical factors from the univariate analysis (PS, liver metastasis, hemoglobin) lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (A + B) (p = 0.005) along with triple negative tumors (p = 0.011) and hemoglobin level (11.5 g/dL) (p = 0.009). Conclusion NDL score combining lymphopenia and reduced TCR diversity seems to be a strong prognostic factor for OS and could be use to improve care quality of MBC patients.
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