Relevance of tumour-infiltrating lymphocytes, PD-1 and PD-L1 in patients with high-risk, nodal-metastasised breast cancer of the German Adjuvant Intergroup Node–positive study

Journal article


Publication Details

Author(s): Noske A, Möbus V, Weber K, Schmatloch S, Weichert W, Köhne CH, Solbach C, Ingold Heppner B, Steiger K, Müller V, Fasching P, Karn T, van Mackelenbergh M, Marmé F, Schmitt WD, Schem C, Stickeler E, Loibl S, Denkert C
Journal: European journal of cancer
Publication year: 2019
Volume: 114
Pages range: 76-88
ISSN: 0959-8049


Abstract

Background: Immune cell infiltration in breast cancer is important for the patient's prognosis and response to systemic therapies including immunotherapy. We sought to investigate the prevalence of tumour-infiltrating lymphocytes (TILs)and their association with immune checkpoints such as programmed cell death 1 (PD-1)and programmed cell death ligand 1 (PD-L1)in high-risk, node-positive breast cancer of the adjuvant German Adjuvant Intergroup Node–positive (GAIN-1)trial. Patients and methods: We evaluated TILs by haematoxylin and eosin staining and PD-1 and PD-L1 (SP263 assay)expression by immunohistochemistry in 1318 formalin-fixed, paraffin-embedded breast carcinomas. The association of TILs with PD-1, PD-L1, molecular intrinsic subtypes, outcome and therapy regimens (dose-dense [dd]epirubicin, paclitaxel and cyclophosphamide [EPC]and dd epirubicin, cyclophosphamide, paclitaxel and capecitabine [EC-PwX])was statistically tested. Results: Overall TILs density was significantly associated with the expression of PD-1 and PD-L1 in immune cells (each p < 0.0001)and PD-L1 in tumour cells (p = 0.0051). TILs were more common in triple-negative breast cancer (TNBC)and human epidermal growth factor receptor 2 (HER2)HER2-positive tumours (each p < 0.0001). On multivariate Cox regression analyses, patients with breast cancer without TILs had an unfavourable disease-free survival (DFS)in the EPC arm compared with the EC-PwX arm (hazard ratio [HR]= 0.69 [0.44–1.06], p = 0.0915); but no differences were seen in tumours with TILs (HR = 1.24 [0.92–1.67], p = 0.1566, interaction p = 0.0336). PD-1–positive immune cells in TNBC were associated with a significantly better DFS (HR = 0.50 [0.25–0.99], p = 0.0457). PD-L1 expression had no impact on patient outcome. Conclusions: TILs predict the benefit of intensified ddEPC compared with ddEC-PwX therapy in node-positive, high-risk breast cancer. TILs, PD-1 and PD-L1 are linked to each other indicating tumour immunogenicity. Moreover, PD-1–positive immune cells have a positive prognostic impact in TNBC. Clinical trial: NCT00196872.


FAU Authors / FAU Editors

Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


External institutions
Deutsches Konsortium für Translationale Krebsforschung (DKTK) Deutsches Krebsforschungszentrum
Elisabeth-Krankenhaus GmbH
GBG Forschungs GmbH (German Breast Group)
Klinikum Oldenburg
Krankenhaus Jerusalem
NeuroCure
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Southern Medical University / 南方医科大学
Universitätsklinikum Frankfurt
Universitätsklinikum Hamburg-Eppendorf


How to cite

APA:
Noske, A., Möbus, V., Weber, K., Schmatloch, S., Weichert, W., Köhne, C.H.,... Denkert, C. (2019). Relevance of tumour-infiltrating lymphocytes, PD-1 and PD-L1 in patients with high-risk, nodal-metastasised breast cancer of the German Adjuvant Intergroup Node–positive study. European journal of cancer, 114, 76-88. https://dx.doi.org/10.1016/j.ejca.2019.04.010

MLA:
Noske, Aurelia, et al. "Relevance of tumour-infiltrating lymphocytes, PD-1 and PD-L1 in patients with high-risk, nodal-metastasised breast cancer of the German Adjuvant Intergroup Node–positive study." European journal of cancer 114 (2019): 76-88.

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Last updated on 2019-23-05 at 06:08