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Breast cancer, metastatic

2847 - A gene signature of chemo-immunization to predict outcome in patients with triple negative breast cancer treated with anthracycline-based neoadjuvant chemotherapy

Date

09 Sep 2017

Session

Breast cancer, metastatic

Topics

Cytotoxic Therapy;  Translational Research;  Breast Cancer

Presenters

Carmen Criscitiello

Citation

Annals of Oncology (2017) 28 (suppl_5): v68-v73. 10.1093/annonc/mdx364

Authors

C. Criscitiello1, M.A. Bayar2, G. Curigliano1, F. Symmans3, C. Desmedt4, H. Bonnefoi5, B. Sinn3, G. Pruneri6, C. Vicier7, J. Pierga8, C. Denkert9, S. Loibl10, C. Sotiriou11, S. Michiels2, F. André12

Author affiliations

  • 1 Division Of Experimental Therapeutics, Istituto Europeo di Oncologia, 20141 - Milan/IT
  • 2 Service De Biostatistique Et D'epidémiologie, Gustave Roussy, 94800 - Villejuif/FR
  • 3 Department Of Pathology, MD Anderson Cancer Center, Houston/US
  • 4 Translational Breast Cancer Laboratory, Institute Jules Bordet, Brussels/BE
  • 5 Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 6 Unità Di Biobank For Translational Medicine, Istituto Europeo di Oncologia, 20141 - Milan/IT
  • 7 Department Of Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 8 Department Of Medical Oncology, institut Curie, 75248 - Paris/FR
  • 9 Institute Of Pathology, Charité Hospital Berlin  , 10117 - Berlin/DE
  • 10 Medicine And Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg/DE
  • 11 Breast Cancer Translational Research Laboratory - Bctl, Institut Jules Bordet, Brussels/BE
  • 12 Breast Cancer Unit, Department Of Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
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Abstract 2847

Background

The extent of tumor-infiltrating lymphocytes (TILs) in the residual disease after anthracycline-based neoadjuvant chemotherapy (NACT) is associated with a better prognosis, in patients with triple-negative breast cancer (TNBC). We aimed to develop a genomic signature from pre-treatment samples to predict the extent of TILs after NACT, and then to test its prognostic value on survival.

Methods

Using 99 pre-treatment samples (training set), we generated a four-gene signature that predicts post-NACT TILs using the LASSO technique. Prognostic value of the signature on survival was first assessed on the training set (n = 99) and then evaluated on an independent validation set including 185 patients with TNBC treated with NACT.

Results

A four-gene signature combining the expression levels of HLF, CXCL13, SULT1E1, and GBP1 predicted the extent of lymphocytic infiltration after NACT. In a multivariate analysis performed on the training set, a one-unit increase in the signature value was associated with distant-relapse free survival (DRFS) (HR: 0.28, 95%CI: 0.13-0.63, p = 0.0018). For the validation dataset, the four-gene signature was significantly associated with DRFS in the entire set (HR: 0.26, 95%CI: 0.11-0.59, p = 0.0012) and in the subset of patients with residual disease (HR: 0.23, 95%CI: 0.10-0.55, p = 0.0008).

Conclusions

We developed a four-gene signature of immune-activation, which predicts outcome in patients treated with NACT for TNBC.

Clinical trial identification

Legal entity responsible for the study

Carmen Criscitiello

Funding

Transcan-2011, Operation Parrain Chercheurs, Odyssea, Fondation Dassault.

Disclosure

All authors have declared no conflicts of interest.

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