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Poster Display session 3

5930 - A transcriptomic immunologic signature predicts favorable outcome in neoadjuvant chemotherapy treated triple negative breast tumors.

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Immunotherapy

Tumour Site

Breast Cancer

Presenters

Javier Pérez-peña

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

J. Pérez-peña1, J.T. Fekete2, R. Páez3, J.A. García-Sáenz4, V. García-Barberán5, P. Pérez-Segura6, A. Pandiella7, B. Gyorffy8, A. Ocaña9, A. Manzano3

Author affiliations

  • 1 Instituto De Biología Molecular Y Celular Del Cáncer, IBSAL - Instituto de Investigación Biomédica de Salamanca, 37007 - Salamanca/ES
  • 2 2nd Department Of Paediatrics, Semmelweiss University-2nd Department of Paediatrics, 1094 - Budapest/HU
  • 3 Medical Oncology Department, Hospital Clínico San Carlos, 28040 - Madrid/ES
  • 4 Medical Oncology, Hospital Clínico San Carlos, 28040 - Madrid/ES
  • 5 Medical Oncology, Hospital Clinico Universitario San Carlos. CIBERONC Instituto de Salud Carlos III, 28040 - Madrid/ES
  • 6 Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 7 Laboratorio 15, Centro de investigación del cáncer, 37007 - Salamanca/ES
  • 8 2nd Department Of Pediatrics, Semmelweis University, 1085 - Budapest/HU
  • 9 Scientific Department, GEICAM, 28703 - San Sebastian de los Reyes/ES

Resources

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Abstract 5930

Background

Limited therapeutic options exist for the treatment of patients with triple negative breast cancer (TNBC) tumors beyond the administration of chemotherapy, and very recently, the approval of the anti PD-L1 inhibitor atezolizumab. Neoadjuvant chemotherapy is currently the standard of care treatment in the early stage disease, although reliable biomarkers of response have been scarcely described. In our study we explored whether immunologic signatures associated with inflamed tumors or hot tumors could predict outcome to neoadjuvant chemotherapy.

Methods

Publicly available transcriptomic data of more than 2,000 patients were evaluated. ROC plots were generated to assess response to therapy. Cox proportional hazards regression was computed to explore the association between gene expression and outcomes. Kaplan-Meier plots were drawn to visualize the survival differences.

Results

Higher expression of IDO1, CXCL9, CXCL10, HLA-DRA, ISGF-3 from the IFN gamma signature, CXCL13, HLA-E, LAG3 and STAT1 from the expanded gene signature and GZMB from the CTL-level signature were associated with higher proportion without relapse in the first five years after chemotherapy in TNBC. The strongest effect was observed for STAT1 (p value =1.8e-05 and AUC 0.69, p = 2.7e-06). The best gene-set signature to predict favorable RFS was the combination of IDO1, LAG3, STAT1 and GZMB (HR 0.28 CI 0.17-0.46 p = 9.8 E-08). However, no influence on pathological complete response (pCR) was observed. Similar, no benefit was identified in any other tumor subtype: HER2 or estrogen receptor positive.

Conclusions

In conclusion, we describe a set of immunologic genes that predict outcome to neoadjuvant chemotherapy in TNBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Instituto de Salud Carlos III.

Disclosure

All authors have declared no conflicts of interest.

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