P2-12-10: Low TCR Diversity (Divpenia) Is a Prognosis Factor of Overall Survival in Metastatic Breast Cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 24_Supplement; pp. P2 - P2-12-10
• Main Authors: Manuel, M, Tredan, O, Bachelot, T, Parmentier, G, Courtier, A, Rabeony, T, Chabaud, S, Mouret, J-F, Grives, A, Perez, S, Clapisson, G, Blay, J-Y, Caux, C, Pasqual, N, Menetrier-Caux, C
• Format: Journal Article
• Language: English
• Published: 15.12.2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS11-P2-12-10

Abstract Background: We already showed that lymphopenia (<1000 lymphocytes/μl) or CD4+ T cell lymphopenia (<450/μl) detected before initiation of chemotherapy are prognostic factors for toxicity and death for metastatic breast cancer (MBC) patients. The goal of the present study was to identify the characteristics of the T cells in these lymphopenic patients. TCR diversity was investigated and tested as a prognostic factor for overall survival (OS). Patients and methods: The ImmunTraCkeR® assay (ImmunID, Grenoble, France), which analyzes through semi quantitative multiplex-PCR the V-D-J combinatorial diversity of TCR-beta chain (TRB), was used to investigate diversity of T cell repertoire on cryopreserved blood samples from a retrospective cohort of MBC patients before chemotherapy administration (n=66). Univariate and multivariate analysis were performed. We then validated our score on a prospective cohort (n=67) using the same eligibility criteria (MBC patients before first line chemotherapy administration). Results: Using a 33% cutoff for divpenia in our retrospective cohort (T cell diversity below 33%) (average diversity for healthy people is 70%), divpenia was associated with a median OS of 10 months vs 22 months for patients with diversity >33% (logrank p value=0.04). The NDL® score (Numeration Diversity Lymphocytes representation) that combines lymphocyte numeration with TRB diversity, demonstrated that lympho-divpenia (T cell diversity below 33% and lymphopenia below lGiga/L) was associated with a poor OS compared to patients with either lymphocyte <1000/μL & diversity >33% or lymphocyte >1000/μL & diversity <33% or both lymphocyte >1000/μL and diversity >33% (p=0.015). In multivariate analysis, including performance status (PS), hemoglobin level, polynuclear neutrophil count (PNN), age, and liver metastasis, NDL® score was identified as an independent prognostic factor for OS. In our prospective validation cohort, NDL® score was also identified as a prognostic factors for OS (p=0,007), as well as lymphopenia (<1000/μL) (p=0,0003), CD4+ lymphopenia (<450/μL) (p=0,04), menopausal status (p=0,02), hormonal receptor status (estrogen receptor p=0.02; progesterone receptor p=0.002) and lung metastasis (p=0,009). In multivariate analysis, hemoglobin level was the only independent prognostic factor in this cohort. Conclusion: We showed that Divpenia and NDL® score are prognostic factors for OS in MBC patients. In order to confirm these results, a prospective clinical trial is ongoing on a larger cohort of MBC and lung cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-10.