Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer.
Recent studies in multiple epithelial cancers have shown that the inhibitory receptor programmed cell death 1 (PD-1) is expressed on tumor-infiltrating lymphocytes and/or programmed death ligand 1 (PD-L1) is expressed on tumor cells, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway. In addition, phase 1 clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 have shown promising results in several human cancers. The purpose of this study was to investigate the impact of PD-L1 expression in human breast cancer specimens. We conducted an immunohistochemistry study using a tissue microarray encompassing 650 evaluable formalin-fixed breast cancer cases with detailed clinical annotation and outcomes data. PD-L1 was expressed in 152 (23.4 %) of the 650 breast cancer specimens. Expression was significantly associated with age, tumor size, AJCC primary tumor classification, tumor grade, lymph node status, absence of ER expression, and high Ki-67 expression. In univariate analysis, PD-L1 expression was associated with a significantly worse OS. In multivariate analysis, PD-L1 expression remained an independent negative prognostic factor for OS. In subset analyses, expression of PD-L1 was associated with significantly worse OS in the luminal B HER2(-) subtype, the luminal B HER2(+) subtype, the HER2 subtype, and the basal-like subtype. This is the first study to demonstrate that PD-L1 expression is an independent negative prognostic factor in human breast cancer. This finding has important implications for the application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease.
Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, CH-4032, Basel, Switzerland, muensts@uhbs.ch.
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S
Muenst
A R
AR
Schaerli
F
F
Gao
S
S
Däster
E
E
Trella
R A
RA
Droeser
M G
MG
Muraro
P
P
Zajac
R
R
Zanetti
W E
WE
Gillanders
W P
WP
Weber
S D
SD
Soysal
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis; D047368:Tumor Burden
D060890:B7-H1 Antigen