Journal Article

Prognostic impact of CD4-positive T cell subsets in early breast cancer: a study based on the FinHer trial patient population

Weyer-Elberich, Veronika, Heimes, Anne-Sophie, Lebrecht, Antje, Schmidt, Marcus, Almstedt, Katrin, Wirtz, Ralph M., Hengstler, Jan G., Fountzilas, George, Battista, Marco J., Sahin, Ugur, Hasenburg, Annette, Kellokumpu-Lehtinen, Pirkko-Liisa, Gerhold-Ay, Aslihan, Kalogeras, Konstantine T., Joensuu, Heikki

2018

Overview

Background The clinical importance of tumor-infiltrating cluster of differentiation 4 (CD4) T cells is incompletely understood in early breast cancer. We investigated the clinical significance of CD4, forkhead box P3 (FOXP3), and B cell attracting chemokine leukocyte chemoattractant-ligand (C-X-C motif) 13 (CXCL13) in early breast cancer. Methods The study is based on the patient population of the randomized FinHer trial, where 1010 patients with early breast cancer were randomly allocated to adjuvant chemotherapy containing either docetaxel or vinorelbine, and human epidermal growth factor receptor 2 (HER2)-positive patients were also allocated to trastuzumab or no trastuzumab. Breast cancer CD4, FOXP3, and CXCL13 contents were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), and their influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates in the entire cohort and in selected molecular subgroups. Interactions between variables were analyzed using Cox regression. The triple-negative breast cancer (TNBC) subset of the HE10/97 randomized trial was used for confirmation. Results High CXCL13 was associated with favorable DDFS in univariable analysis, and independently in multivariable analysis (HR 0.44, 95% CI 0.29–0.67, P ≤ 0.001), most strongly in TNBC (HR 0.39, 95% CI 0.19–0.79, P = 0.009). No significant interaction with chemotherapy or trastuzumab administration was detected. Neither tumor CD4 content nor FOXP3 content was associated with DDFS. The favorable prognostic influence of CXCL13 was confirmed in the HE10/97 trial patient population with TNBC (HR 0.30, 95% CI 0.09–0.93; P = 0.038). Conclusions The results provide a high level of evidence that humoral immunity influences the survival outcomes of patients with early breast cancer, in particular of those with TNBC. Trial registration The study reports retrospective biomarker analyses in the prospective FinHer trial and the prospective HE10/97 trial. ISRCTN76560285 . Registered on 18 March 2005. ACTRN12611000506998 . Registered on 16 May 2011.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adult / Aged / Analysis / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Biomedicine / Breast cancer / Cancer Research / Care and treatment / CD4 Antigens - genetics / CD4-Positive T-Lymphocytes / Chemokine CXCL13 - genetics / Chemotherapy, Adjuvant - adverse effects / Disease-Free Survival / Docetaxel - administration & dosage / Female / Forkhead Transcription Factors - genetics / Humans / Humoral / Immune system / Lymphocytes / Lymphocytes, Tumor-Infiltrating - drug effects / Middle Aged / Oncology / Prognosis / Research Article / Surgical Oncology / T cells / Trastuzumab - administration & dosage / Triple Negative Breast Neoplasms - drug therapy / Triple Negative Breast Neoplasms - genetics / Triple Negative Breast Neoplasms - pathology / Tumor-infiltrating lymphocytes / Vinorelbine - administration & dosage