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Evaluation of tumor-infiltrating lymphocytes, PD-L1, and PIK3CA mutations and association with prognosis in HER2-positive early stage breast cancer.

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  • معلومة اضافية
    • المصدر:
      Publisher: Medical Journals Sweden AB Country of Publication: England NLM ID: 8709065 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1651-226X (Electronic) Linking ISSN: 0284186X NLM ISO Abbreviation: Acta Oncol Subsets: MEDLINE
    • بيانات النشر:
      Publication: 2024- : [Uppsala, Sweden] : Medical Journals Sweden AB
      Original Publication: Stockholm, Sweden : Acta Oncologica, [1987-
    • الموضوع:
      Breast Neoplasms*/pathology; Humans ; Female ; B7-H1 Antigen/genetics ; B7-H1 Antigen/metabolism ; Lymphocytes, Tumor-Infiltrating/pathology ; Prognosis ; Class I Phosphatidylinositol 3-Kinases/genetics ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Tumor Microenvironment
    • نبذة مختصرة :
      Background: Tumor-infiltrating lymphocytes (TILs) have predictive and prognostic potential in HER2-positive breast cancer (HER2+ BC). Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein, with important roles in the tumor microenvironment, possibly in both tumor and immune cells (ICs), providing rationale for targeting with immune-checkpoint therapy. PIK3CA mutations are oncogenic, activating mutations, which are also of relevance in breast cancer. Herein, we investigate the frequency of TILs, PD-L1 and PIK3CA mutations, and whether these factors influence outcome, in early HER2+ BC.
      Materials and Methods: Stromal TILs (sTILs) and PD-L1 expressions were assessed using full tumor-sections and TMA, respectively, from 236 patients with HER2+ BC. TILs were assessed, according to a standardized method, as continuous measurement and according to three predefined categories: low (0-10%), intermediate (11-59%), and high (60-100%). PD-L1 immunohistochemistry (Ventana SP263) was evaluated and positivity defined as ≥1% expression in tumor and ICs. PIK3CA mutations (exons 9 and 20) were determined by pyrosequencing.
      Results: Fourteen percent of patients had high sTILs and 25% had a PIK3CA mutation. PD-L1 expression was more frequent in ICs (68%) than tumor cells (24%). Patients with low sTILs had a significantly worse overall survival (multivariate: HR 2.80; 95% CI 1.36-5.78; p  = .02).
      Discussion: Patients with low sTILs had a significantly poorer survival, despite adequate treatment with adjuvant therapy.
    • Contributed Indexing:
      Keywords: HER2-positive breast cancer; PD-L1; PIK3CA mutation; TILs; tumor-infiltrating lymphocytes
    • الرقم المعرف:
      0 (CD274 protein, human)
      0 (B7-H1 Antigen)
      EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
      0 (Biomarkers, Tumor)
      EC 2.7.1.137 (PIK3CA protein, human)
    • الموضوع:
      Date Created: 20231114 Date Completed: 20231127 Latest Revision: 20231127
    • الموضوع:
      20231215
    • الرقم المعرف:
      10.1080/0284186X.2023.2279685
    • الرقم المعرف:
      37961947