Login
- 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.
- Document type:
- Journal Article
- Author(s):
- 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; Marme, Frederik; Schmitt, Wolfgang D; Schem, Christian; Stickeler, Elmar; Loibl, Sybille; Denkert, Carsten
- 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.
- Journal title abbreviation:
- Eur J Cancer
- Year:
- 2019
- Journal volume:
- 114
- Pages contribution:
- 76-88
- Fulltext / DOI:
- doi:10.1016/j.ejca.2019.04.010
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/31075727
- Print-ISSN:
- 0959-8049
- TUM Institution:
- Institut für Allgemeine Pathologie und Pathologische Anatomie
BibTeX