Mutation and immune profiling of metaplastic breast cancer: Correlation with survival

• Published in: PloS one Vol. 14; no. 11; p. e0224726
• Main Authors: Afkhami, Michelle, Schmolze, Daniel, Yost, Susan E, Frankel, Paul H, Dagis, Andrew, Amanam, Idoroenyi U, Telatar, Milhan, Nguyen, Kim, Yu, Kim Wai, Luu, Thehang, Pillai, Raju, Aoun, Patricia A, Mortimer, Joanne, Yuan, Yuan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06-11-2019; Public Library of Science (PLoS)
• Subjects: AACR; Adult; Aged; Aged, 80 and over; Atezolizumab; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Bevacizumab; Biology and life sciences; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Breast - pathology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer research; Cancer therapies; CD3 antigen; CD4 antigen; CD8 antigen; Chemotherapy; Class I Phosphatidylinositol 3-Kinases - genetics; Death; Development and progression; Disease-Free Survival; DNA Mutational Analysis; Epithelium - pathology; Everolimus; Female; Gene expression; Gene Expression Regulation, Neoplastic - immunology; Genes; Genetic aspects; Genetic research; Health risk assessment; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Immunotherapy; Ligands; Medical diagnosis; Medical equipment industry; Medical prognosis; Medical research; Medicine and Health Sciences; Metastasis; Middle Aged; Mutation; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - immunology; Next-generation sequencing; Oncology; p53 Protein; Pathology; Patients; PD-L1 protein; Profiling; Prognosis; PTEN Phosphohydrolase - genetics; PTEN protein; Radiation therapy; Regression analysis; Research and Analysis Methods; Retrospective Studies; Survival; Survival analysis; Temsirolimus; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumors; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0224726

The goal of this study is to characterize the genomic and immune profiles of metaplastic breast cancer (MpBC) and identify the association with survival through an analysis of archived tumor tissue. A next-generation sequencing-based mutational assay (Onco-48) was performed for 21 MpBC patients. Clinicopathologic characteristics were captured, including relapse free survival (RFS) and overall survival (OS). Immunohistochemistry (IHC) for CD3, CD4, CD8, and programmed death-ligand 1 (PD-L1) was also performed. Recurrence free survival (RFS) at 5 years was 57% (95% CI 0.34-0.75) and overall survival (OS) at 5 years was 66% (95% CI 0.41-0.82). The most commonly altered genes were TP53 (68.4%, 13/19), PIK3CA (42.1%, 8/19), and PTEN (15.8%, 3/19. For patients with PIK3CA mutations, RFS and OS were significantly worse than for those without (HR 5.6, 95% CI 1.33-23.1 and HR 8.0, 95% CI 1.53-41.7, respectively). Cox regression estimated that PD-L1 expression was associated with worse RFS and OS (HR 1.08, 95% CI 1.01-1.16 and HR 1.05, 95% CI 1.00-1.11, respectively, for an absolute increase in PD-L1 expression of 1%). In conclusion, PIK3CA mutation and PD-L1 expression confer poor prognosis in this cohort of patients with MpBC.