Prognostic and predictive value of PDL1 expression in breast cancer

Abstract

// Renaud Sabatier 1,2,3 , Pascal Finetti 1 , Emilie Mamessier 1 , José Adelaide 1 , Max Chaffanet 1 , Hamid Raza Ali 4,5 , Patrice Viens 1,2,3 , Carlos Caldas 5 , Daniel Birnbaum 1 and François Bertucci 1,2,3 1 Département d’Oncologie Moléculaire, “Equipe labellisée Ligue Contre le Cancer”, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France 2 Département d’Oncologie Médicale, CRCM, Institut Paoli-Calmettes, Marseille, France 3 Faculté de Médecine, Aix-Marseille Université, Marseille, France 4 Department of Pathology, University of Cambridge, Cambridge, United Kingdom 5 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom Correspondence: François Bertucci, email: // Keywords : breast cancer, chemotherapy, immune response, PDL1, survival Received : November 17, 2014 Accepted : December 26, 2014 Published : December 31, 2014 Abstract Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in breast cancer. Recently PD1/PDL1-inhibitors have shown promising results in different carcinomas with correlation between PDL1 tumor expression and responses. We retrospectively analyzed PDL1 mRNA expression in 45 breast cancer cell lines and 5,454 breast cancers profiled using DNA microarrays. Compared to normal breast samples, PDL1 expression was upregulated in 20% of clinical samples and 38% of basal tumors. High expression was associated with poor-prognosis features (large tumor size, high grade, ER-negative, PR-negative, ERBB2- positive status, high proliferation, basal and ERBB2 -enriched subtypes). PDL1 upregulation was associated with biological signs of strong cytotoxic local immune response. PDL1 upregulation was not associated with survival in the whole population, but was associated with better metastasis-free and overall specific survivals in basal tumors, independently of clinicopathological features. Pathological complete response after neoadjuvant chemotherapy was higher in case of PDL1 upregulation (50% versus 21%). In conclusion, PDL1 upregulation, more frequent in basal breast cancers, was associated with increased T-cell cytotoxic immune response. In this aggressive subtype, upregulation was associated with better survival and response to chemotherapy. Reactivation of dormant tumor-infiltrating lymphocytes by PDL1-inhibitors could represent promising strategy in PDL1-upregulated basal breast cancer.