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Publications

Journal Article Research Support, Non-U.S. Gov't Ppublish 11 citations

PubMed: 35759853 DOI: 10.1016/j.esmoop.2022.100502

An immunological signature to predict outcome in patients with triple-negative breast cancer with residual disease after neoadjuvant chemotherapy.

ESMO Open 7(4):100502

Authors: C Blaye, É Darbo, M Debled, V Brouste, V Vélasco, C Pinard, N Larmonier, I Pellegrin, A Tarricone, M Arnedos, J Commeny, H Bonnefoi, C Larmonier, G MacGrogan

Affiliations

  • Department of Medical Oncology, Institut Bergonié, Bordeaux, France; Univ. Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, Bordeaux, France.
  • Univ. Bordeaux, INSERM U1218, ACTION Laboratory, Bordeaux, France.
  • Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
  • Departments of Clinical Research and Medical Information, Bordeaux, France.
  • Biopathology, Institut Bergonié, Bordeaux, France.
  • Pathology Laboratory, University Hospital of Martinique, Fort de France.
  • Univ. Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, Bordeaux, France; Univ. Bordeaux, Bordeaux, France.
  • Service d'Immunologie et Immunogénétique, University Hospital of Bordeaux, Bordeaux, France; Centre de Ressources Biologiques Plurithématique, University Hospital of Bordeaux, Bordeaux, France.
  • Service d'Immunologie et Immunogénétique, University Hospital of Bordeaux, Bordeaux, France.
  • Department of Surgery, Institut Bergonié, Bordeaux, France.
  • Department of Medical Oncology, Institut Bergonié, Bordeaux, France; Univ. Bordeaux, INSERM U1218, ACTION Laboratory, Bordeaux, France; Univ. Bordeaux, Bordeaux, France.
  • Univ. Bordeaux, INSERM U1218, ACTION Laboratory, Bordeaux, France; Biopathology, Institut Bergonié, Bordeaux, France.

Abstract

BACKGROUND

When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post-NACT samples to predict relapse.

MATERIALS AND METHODS

We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the NanoString PanCancer IO360 panel to develop a prognostic transcriptomic signature, and we describe the immune microenvironments of the residual tumors.

RESULTS

Thirty-eight (33%) patients experienced metastatic relapse. Hierarchical clustering separated patients into five clusters with distinct prognosis based on pathways linked to immune activation, epithelial-to-mesenchymal transition and cell cycle. The immune microenvironment of the residual disease was significantly different between patients who experienced relapse compared to those who did not, the latter having significantly more effector antitumoral immune cells, with significant differences in lymphoid subpopulations. We selected eight genes linked to immunity (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a transcriptomic signature which could predict relapse in our cohort. This signature was validated in two external cohorts (KMplot and METABRIC).

CONCLUSIONS

Lack of immune activation after NACT is associated with a high risk of distant relapse. We propose a prognostic signature based on immune infiltrate that could lead to targeted therapeutic strategies to improve patient prognosis.

MeSH

Neoplasm, Residual, Risk, Prognosis, Drug Therapy, Triple Negative Breast Neoplasms, Cells, Therapeutics, Genes, Chemotherapy

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