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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

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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. / Noske, Aurelia; Möbus, Volker; Weber, Karsten; Schmatloch, Sabine; Weichert, Wilko; Köhne, Claus-Henning; Solbach, Christine; Ingold Heppner, Barbara; Steiger, Katja; Müller, Volkmar; Fasching, Peter; Karn, Thomas; van Mackelenbergh, Marion; Marmé, Frederik; Schmitt, Wolfgang D; Schem, Christian; Stickeler, Elmar; Loibl, Sybille; Denkert, Carsten.

in: EUR J CANCER, Jahrgang 114, 06.2019, S. 76-88.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Noske, A, Möbus, V, Weber, K, Schmatloch, S, Weichert, W, Köhne, C-H, 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 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', EUR J CANCER, Jg. 114, S. 76-88. https://doi.org/10.1016/j.ejca.2019.04.010

APA

Noske, A., Möbus, V., Weber, K., Schmatloch, S., Weichert, W., Köhne, C-H., Solbach, C., Ingold Heppner, B., Steiger, K., Müller, V., Fasching, P., Karn, T., van Mackelenbergh, M., Marmé, F., Schmitt, W. D., Schem, C., Stickeler, E., Loibl, S., & 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. EUR J CANCER, 114, 76-88. https://doi.org/10.1016/j.ejca.2019.04.010

Vancouver

Noske A, Möbus V, Weber K, Schmatloch S, Weichert W, Köhne C-H 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. EUR J CANCER. 2019 Jun;114:76-88. https://doi.org/10.1016/j.ejca.2019.04.010

Bibtex

@article{e95da92929d246279596a3463de868d6,
title = "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",
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)-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.",
keywords = "Adult, Biomarkers, Tumor/metabolism, Chemotherapy, Adjuvant/methods, Female, Germany, Humans, Lymphocytes, Tumor-Infiltrating/immunology, Middle Aged, Prognosis, Programmed Cell Death 1 Receptor/therapeutic use, Prospective Studies, Triple Negative Breast Neoplasms/drug therapy",
author = "Aurelia Noske and Volker M{\"o}bus and Karsten Weber and Sabine Schmatloch and Wilko Weichert and Claus-Henning K{\"o}hne and Christine Solbach and {Ingold Heppner}, Barbara and Katja Steiger and Volkmar M{\"u}ller and Peter Fasching and Thomas Karn and {van Mackelenbergh}, Marion and Frederik Marm{\'e} and Schmitt, {Wolfgang D} and Christian Schem and Elmar Stickeler and Sybille Loibl and Carsten Denkert",
note = "Copyright {\textcopyright} 2019 Elsevier Ltd. All rights reserved.",
year = "2019",
month = jun,
doi = "10.1016/j.ejca.2019.04.010",
language = "English",
volume = "114",
pages = "76--88",
journal = "EUR J CANCER",
issn = "0959-8049",
publisher = "Elsevier Limited",

}

RIS

TY - JOUR

T1 - 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

AU - Noske, Aurelia

AU - Möbus, Volker

AU - Weber, Karsten

AU - Schmatloch, Sabine

AU - Weichert, Wilko

AU - Köhne, Claus-Henning

AU - Solbach, Christine

AU - Ingold Heppner, Barbara

AU - Steiger, Katja

AU - Müller, Volkmar

AU - Fasching, Peter

AU - Karn, Thomas

AU - van Mackelenbergh, Marion

AU - Marmé, Frederik

AU - Schmitt, Wolfgang D

AU - Schem, Christian

AU - Stickeler, Elmar

AU - Loibl, Sybille

AU - Denkert, Carsten

N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.

PY - 2019/6

Y1 - 2019/6

N2 - 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)-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.

AB - 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)-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.

KW - Adult

KW - Biomarkers, Tumor/metabolism

KW - Chemotherapy, Adjuvant/methods

KW - Female

KW - Germany

KW - Humans

KW - Lymphocytes, Tumor-Infiltrating/immunology

KW - Middle Aged

KW - Prognosis

KW - Programmed Cell Death 1 Receptor/therapeutic use

KW - Prospective Studies

KW - Triple Negative Breast Neoplasms/drug therapy

U2 - 10.1016/j.ejca.2019.04.010

DO - 10.1016/j.ejca.2019.04.010

M3 - SCORING: Journal article

C2 - 31075727

VL - 114

SP - 76

EP - 88

JO - EUR J CANCER

JF - EUR J CANCER

SN - 0959-8049

ER -