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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.
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.
- Source :
-
European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2019 Jun; Vol. 114, pp. 76-88. Date of Electronic Publication: 2019 May 07. - Publication Year :
- 2019
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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.<br />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.<br />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.<br />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.<br />Clinical Trial: NCT00196872.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adult
Biomarkers, Tumor metabolism
Female
Germany
Humans
Middle Aged
Prognosis
Prospective Studies
Triple Negative Breast Neoplasms drug therapy
Triple Negative Breast Neoplasms pathology
Chemotherapy, Adjuvant methods
Lymphocytes, Tumor-Infiltrating immunology
Programmed Cell Death 1 Receptor therapeutic use
Triple Negative Breast Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0852
- Volume :
- 114
- Database :
- MEDLINE
- Journal :
- European journal of cancer (Oxford, England : 1990)
- Publication Type :
- Academic Journal
- Accession number :
- 31075727
- Full Text :
- https://doi.org/10.1016/j.ejca.2019.04.010