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Breast Cancer Research and Treatment

, Volume 151, Issue 3, pp 619–627 | Cite as

Prognostic and predictive value of NanoString-based immune-related gene signatures in a neoadjuvant setting of triple-negative breast cancer: relationship to tumor-infiltrating lymphocytes

  • Hee Jin Lee
  • Jeong-Ju Lee
  • In Hye Song
  • In Ah Park
  • Jun Kang
  • Jong Han Yu
  • Jin-Hee Ahn
  • Gyungyub GongEmail author
Clinical Trial

Abstract

The prognostic significance of tumor-infiltrating lymphocytes and immune signals has been described previously in triple-negative breast cancer (TNBC). Furthermore, recent studies have shown that immunologic parameters are relevant for the response to neoadjuvant chemotherapy (NAC) in breast cancer as well as for outcomes after adjuvant chemotherapy. However, immune signals are variable, and which signals are important is largely unknown. We, therefore, evaluated the expression of immune-related genes in TNBC treated with NAC. We retrospectively evaluated biopsy tissue from 55 patients with primary TNBC treated with NAC (anthracycline, cyclophosphamide, and docetaxel) against the NanoString nCounter GX Human Immunology Panel (579 immune-related genes). Higher expression of cytotoxic molecules, T cell receptor signaling pathway components, cytokines related to T helper cell type 1 (Th1), and B cell markers was associated with a pathologic complete response (pCR). Higher expression of NFKB1, MAPK1, TRAF1, CXCL13, GZMK, and IL7R was significantly associated with pCR, higher Miller-Payne grade, and lower residual cancer burden class. Expression of NFKB1, TRAF1, and CXCL13genes, in particular, was significantly correlated with a longer disease-free survival rate. Conversely, patients those who failed to achieve a pCR showed increased expression of genes related to neutrophils. Higher expression of cytotoxic molecules, T cell receptor signaling pathway components, Th1-related cytokines, and B cell markers is correlated with pCR and survival in TNBC patients treated with NAC. Our results suggest that the activation status of neutrophils may provide additional predictive information for TNBC patients treated with NAC.

Keywords

Triple-negative breast cancer Prognosis Tumor-infiltrating lymphocytes NanoString 

Notes

Acknowledgments

This study was supported by a grant (2013-0866) from the Asan Institute for Life Sciences, Seoul, Korea. We thank professor Chan Sik Park, Asan Medical Center for comments that greatly improved the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10549_2015_3438_MOESM1_ESM.pdf (62 kb)
Supplementary material 1 (PDF 61 kb)
10549_2015_3438_MOESM2_ESM.pdf (123 kb)
Supplementary material 2 (PDF 123 kb)
10549_2015_3438_MOESM3_ESM.pdf (32 kb)
Supplementary material 3 (PDF 32 kb)
10549_2015_3438_MOESM4_ESM.pdf (91 kb)
Supplementary material 4 (PDF 91 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Hee Jin Lee
    • 1
  • Jeong-Ju Lee
    • 2
  • In Hye Song
    • 1
  • In Ah Park
    • 1
  • Jun Kang
    • 3
  • Jong Han Yu
    • 4
  • Jin-Hee Ahn
    • 5
  • Gyungyub Gong
    • 1
    Email author
  1. 1.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Department of PathologyMyongji HospitalGoyangKorea
  3. 3.Department of Pathology, Incheon St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaIncheonKorea
  4. 4.Department of Surgery, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  5. 5.Department of OncologyUniversity of Ulsan College of Medicine, Asan Medical CenterSeoulKorea

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