Abstract
Purpose
The purpose of the study was to evaluate protein expression of PD-L1 and CD20 as prognostic biomarkers of patient outcome in inflammatory breast cancer (IBC) samples.
Methods
PD-L1 and CD20 protein expression was measured by immunohistochemistry in 221 pretreatment IBC biopsies. PD-L1 was assessed in tumor cells (PD-L1+ tumor cells) and tumor stromal infiltrating lymphocytes (PD-L1+ TILs); CD20 was scored in tumor-infiltrating B cells. Kaplan–Meier curves and Cox proportional hazard models were used for survival analysis.
Results
PD-L1+ tumor cells, PD-L1+ TILs, and CD20+ TILs were found in 8%, 66%, and 62% of IBC, respectively. PD-L1+ tumor cells strongly correlated with high TILs, pathological complete response (pCR), CD20+ TILs, but marginally with breast cancer-specific survival (BCSS, P = 0.057). PD-L1+ TILs strongly correlated with high TILs, CD20+ TILs, and longer disease-free survival (DFS) in all IBC and in triple-negative (TN) IBC (P < 0.035). IBC and TN IBC patients with tumors containing both CD20+ TILs and PD-L1+ TILs (CD20+TILs/PD-L1+TILs) showed longer DFS and improved BCSS (P < 0.002) than patients lacking both, or those with either CD20+ TILs or PD-L1+ TILs alone. In multivariate analyses, CD20+TILs/PD-L1+TILs status was an independent prognostic factor for DFS in IBC (hazard ratio (HR): 0.53, 95% CI 0.37–0.77) and TN IBC (HR: 0.39 95% CI 0.17–0.88), and for BCSS in IBC (HR: 0.60 95% CI 0.43–0.85) and TN IBC (HR: 0.38 95% CI 0.17–0.83).
Conclusion
CD20+TILs/PD-L1+TILs status represents an independent favorable prognostic factor in IBC and TN IBC, suggesting a critical role for B cells in antitumor immune responses. Anti-PD-1/PD-L1 and B cell-activating immunotherapies should be explored in these settings.
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Abbreviations
- IBC:
-
Inflammatory breast cancer.
- TN:
-
Triple-negative.
- PD-1:
-
Programmed cell death 1.
- PD-L1:
-
Programmed cell death ligand 1.
- TILs:
-
Tumor-infiltrating lymphocytes.
- pCR:
-
Pathological complete response.
- BCSS:
-
Breast cancer-specific survival.
- DFS:
-
Disease-free survival.
- HR:
-
Hazard ratio.
- CI:
-
Confidential interval.
- NACT:
-
Neoadjuvant chemotherapy.
- FFPETs:
-
Formalin-fixed paraffin embedded tissues.
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Acknowledgements
This study was supported in part by the GlaxoSmithKline Oncology Ethnic Research Initiative Grant (Drs. Arias-Pulido and Chaher; no grant number), and the UICC ICRETT fellowship (Dr. Chaher; ICR/09/043), and the National Institutes of Health (Dr. Prossnitz; CA163890). We would like to thank the PMCCC Human Tissue Repository for providing tissue samples and clinical data (Algiers, Algeria); Karen Buehler (Tricore, NM) for technical support with IHC. The authors thank Dr. J. Louise Lines of the Department of Microbiology and Immunology, Norris Cotton Cancer Center Geisel School of Medicine at Dartmouth for critical reading of this manuscript and insightful comments, Donald Fitzpatrick (Computing and Media Services; Dartmouth Biomedical Libraries) for help with the graphs, and Mrs. Kathleen Bryar for her editorial assistance.
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LAE receives research funding from Genentech, Roche, EMD Serono, Merck, Astra Zeneca, and Corvus. She has served on advisory boards for Astrazeneca, Medimmune, Syndax, Bayer, and Abbvie. ACM receives research funding from Bristol-Myers Squibb. The remaining authors declare no conflict of interest.
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10549_2018_4834_MOESM1_ESM.tif
Fig. S1. The presence of CD20+ TILs is associated with improved DFS, but not BCSS in IBC patients. Kaplan-Meier survival estimates of DFS (a) and BCSS (b) in IBC patients with positive (≥1%) CD20+ TILs compared to negative (<1%) CD20+ TILs. The number of patients at risk of death and/or relapse from IBC are shown at 0, 12, 24, 36, 48, 72, 84, and 96 months below the x axis. Supplementary material 1 (TIFF 3187 KB)
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Arias-Pulido, H., Cimino-Mathews, A., Chaher, N. et al. The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome. Breast Cancer Res Treat 171, 273–282 (2018). https://doi.org/10.1007/s10549-018-4834-7
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DOI: https://doi.org/10.1007/s10549-018-4834-7