Abstract 62P
Background
Immune checkpoint inhibitors are now a part of the treatment arsenal for triple-negative breast cancer (TNBC) but refinement of PD-L1 as a prognostic and predictive biomarker in TNBC is a clinical priority. We aimed to evaluate the relevance of novel PD-L1 immunohistochemical (IHC) thresholds with regards to prognostic value, PD-L1 gene expression and TNBC molecular subtypes.
Methods
We evaluated PD-L1 on a tissue microarray with the SP142 (immune cell score; IC) and 22C3 (combined positive score; CPS) IHC assays and scored abundance of TILs on H&E sections in a population-based cohort of 237 early-stage TNBC patients diagnosed from 2010 to 2015. The majority of the patients were treated with adjuvant chemotherapy and none received checkpoint inhibitors. Survival analysis was performed (overall survival, invasive disease-free survival, distant relapse-free interval) and RNA sequencing data employed for molecular profiling.
Results
As expected, PD-L1 positivity (IC≥1%; CPS ≥1) was significantly associated with better prognosis compared to zero PD-L1 expression. Importantly however, also patients with intermediate expression (IC >0%, <1%; CPS >0, <1) showed a trend towards improved outcome for all the endpoints. Tumors with intermediate IHC expression also had intermediate PD-L1 (CD274) gene expression (mRNA). Patients low in TILs (<30%) and PD-L1 tended to have the poorest prognosis. PD-L1 positive tumors clustered significantly more often as Immunomodulatory-high and Basal-Like 1-high TNBC subtypes. PD-L1-zero tumors were more prevalently of the Luminal-Androgen-Receptor-high, Mesenchymal-high and Mesenchymal Stem-like-high molecular subtypes. PD-L1-intermediate tumors categorized with neither PD-L1-positive nor PD-L1-zero tumors on the hierarchical clustering level, forming thus a unique subgroup.
Conclusions
With both SP142 and 22C3, we identified an intermediate IHC PD-L1 group within TNBCs that was supported on the molecular level. Any PD-L1 IHC expression, even though it is <1, tended to have positive prognostic impact. We suggest that the generally accepted threshold of PD-L1 IHC positivity in TNBC should be investigated further.
Clinical trial identification
NCT02306096.
Legal entity responsible for the study
The authors.
Funding
The study was made possible through support from the Mrs. Berta KampradFoundation, Governmental and Regjonal Funding of Research within the Swedish National Health Service (ALF and Regional PhD grant), Swedish Breast Cancer Association, the Swedish Cancer Society (Cancerfonden), Region Skåne, Anna-Lisa and Sven-Erik LundgrenFoundation, the Anna and Edwin BergerFoundation, Lund University Research Foundation, Skåne University Hospital Research Foundation and the Marcus and Marianne WallenbergFoundation.
Disclosure
J. Hartman: Financial Interests, Institutional, Research Grant, Has received institutional research support from Cepheid, Roche and Novartis: Cepheid, Roche and Novartis; Other, Personal, Ownership Interest, Is a co-founder and shareholder of Stratipath AB: Stratipath AB; Financial Interests, Personal and Institutional, Advisory Board, Has obtained speaker’s honoraria or advisory board remunerations from Roche, Novartis, Pfizer, Eli Lilly, MSD, Veracyte and Exact Sciences: Roche, Novartis, Pfizer, Eli Lilly, MSD, Veracyte and Exact Sciences. All other authors have declared no conflicts of interest.