TNBC – triple-negative mammary carcinomas
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Studies have shown that patients with triple-negative mammary carcinomas (TNBC) can benefit from immunotherapy in combination with chemotherapy as a first-line therapy.1,2 Since November 2021, authorization has been granted to two drugs (atezolizumab and pembrolizumab) that have a PD-L1 status as a precondition for their administration.
Please refer to the table below for the state of play on authorization:
|Female genital tract|
Last Update: 12. January 2023
As of this writing, there are two scores relevant for authorization and their associated cut-offs, which we must specify for TNBC. For the administration of atezolizumab, an Immune Cell (IC) score with a cut-off of ≥1% is required.
For the administration of pembrolizumab in combination with chemotherapy, a CPS ≥10 is required. Please also refer to the new AGO recommendation
IC is an area score, which we have already met in the context of urothelial carcinomas. With this score, it is important that the PD-L1-positive immune cells are placed in relation to the tumor area. Lymphocytes, macrophages, dendritic cells, and granulocytes are all included in the evaluation. Please note that immune cells located in necrotic areas are excluded from the evaluation.
The percentage is scored as follows (the percent sign must not be omitted):
IC 0: 0 to <1%
IC 1: ≥1% to <5%
IC 2: 5% to <10%
IC 3: ≥10%
Immune cells are understood to include lymphocytes and macrophages. Granulocytes and plasma cells are excluded from evaluation. The reader is expressly reminded that PD-L1-positive immune cells are also placed in relation to viable tumor cells.
Interpretation guidance for IC
A guide for TNBC is available as an aid to interpretation. Please note that this guide relates to SP142.
PD-L1 prevalence in TNBC
In accordance with current study data3 for TNBC, prevalence for IC is
IC 1: ≥1% to <5% = 27%
IC 2/3: ≥5% = 14%
Study data4 for TNBC show the following prevalences for CPS:
CPS>1 = 80%
CPS>10 = 38%
Test system validation/antibody selection in TNBC
The studies performed for atezolizumab with the IC score used the study antibody SP142. As LDTs are often used in Europe – and Germany in particular – it is important that the antibodies are established, validated, and verified according to guidance published by the German Accreditation Body (DAkkS). From the data, we know that either benign human tonsil or cell lines are used as suitable controls.
Alongside SP142, many other antibodies also show good immune cell presentation. As already mentioned in the other indication modules on the PD-L1 Portal, SP-142 exhibits a weakness in PD-L1 detection on tumor cells. As a result, while IC with SP142 can be determined effectively, it is not sufficient for determining the CPS. This also recently been demonstrated in a study by Noske et al.5
QuIP Proficiency Test PD-L1 TNBC
- Cortés, J. et al. IMpassion132 Phase III trial: atezolizumab and chemotherapy in early relapsing metastatic triple-negative breast cancer. Future Oncology15, 1951–1961 (2019).
- Schmid, P. et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology21, 44–59 (2020).
- Noske, A. et al. A multicentre analytical comparison study of inter‐reader and inter‐assay agreement of four programmed death‐ligand 1 immunohistochemistry assays for scoring in triple‐negative breast cancer. Histopathology78, 567–577 (2021).
- Cortes, J. et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Journal of Clinical Oncology38, 1000 (2020).
- Noske, A. et al. Interassay and interobserver comparability study of four programmed death-ligand 1 (PD-L1) immunohistochemistry assays in triple-negative breast cancer. The Breast60, 238–244 (2021).