A signature of immune function genes associated with recurrence-free survival in breast cancer patients

Maria Libera Ascierto, MacIej Kmieciak, Michael O. Idowu, Rose Manjili, Yingdong Zhao, Margaret Grimes, Catherine Dumur, Ena Wang, Viswanathan Ramakrishnan, Xiang Yang Wang, Harry D. Bear, Francesco M. Marincola, Masoud H. Manjili

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81 Citations (Scopus)

Abstract

The clinical significance of tumor-infiltrating immune cells has been reported in a variety of human carcinomas including breast cancer. However, molecular signature of tumor-infiltrating immune cells and their prognostic value in breast cancer patients remain elusive. We hypothesized that a distinct network of immune function genes at the tumor site can predict a low risk versus high risk of distant relapse in breast cancer patients regardless of the status of ER, PR, or HER-2/neu in their tumors. We conducted retrospective studies in a diverse cohort of breast cancer patients with a 1-5 year tumor relapse versus those with up to 7 years relapse-free survival. The RNAs were extracted from the frozen tumor specimens at the time of diagnosis and subjected to microarray analysis and real-time RT-PCR. Paraffin-embedded tissues were also subjected to immunohistochemistry staining. We determined that a network of immune function genes involved in B cell development, interferon signaling associated with allograft rejection and autoimmune reaction, antigen presentation pathway, and cross talk between adaptive and innate immune responses were exclusively upregulated in patients with relapse-free survival. Among the 299 genes, five genes which included B cell response genes were found to predict with >85% accuracy relapse-free survival. Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel. These data suggest that neoadjuvant immunotherapy in patients with high risk of relapse may reduce tumor recurrence by inducing the immune function genes.

Original languageEnglish
Pages (from-to)871-880
Number of pages10
JournalBreast Cancer Research and Treatment
Volume131
Issue number3
DOIs
Publication statusPublished - Feb 2012
Externally publishedYes

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Keywords

  • Breast cancer prognosis
  • Immune response
  • Neoadjuvant immunotherapy
  • Tumor microenvironment
  • Tumor relapse

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ascierto, M. L., Kmieciak, M., Idowu, M. O., Manjili, R., Zhao, Y., Grimes, M., Dumur, C., Wang, E., Ramakrishnan, V., Wang, X. Y., Bear, H. D., Marincola, F. M., & Manjili, M. H. (2012). A signature of immune function genes associated with recurrence-free survival in breast cancer patients. Breast Cancer Research and Treatment, 131(3), 871-880. https://doi.org/10.1007/s10549-011-1470-x