The Immunologic Constant of Rejection Classification Refines the Prognostic Value of Conventional Prognostic Signatures in Breast Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2018 Oct 25

PMID 30353048

Citations 39

Authors

Francois Bertucci

Pascal Finetti

Ines Simeone

Wouter Hendrickx

Ena Wang

Francesco M Marincola

Patrice Viens

Emilie Mamessier

Michele Ceccarelli

Daniel Birnbaum

Davide Bedognetti

Affiliations

Soon will be listed here.

Abstract

Background: The immunologic constant of rejection (ICR) is a broad phenomenon of Th-1 immunity-mediated, tissue-specific destruction.

Methods: We tested the prognostic value of a 20-gene ICR expression signature in 8766 early breast cancers.

Results: Thirty-three percent of tumours were ICR1, 29% ICR2, 23% ICR3, and 15% ICR4. In univariate analysis, ICR4 was associated with a 36% reduction in risk of metastatic relapse when compared with ICR1-3 (p = 2.30E-03). In multivariate analysis including notably the three major prognostic signatures (Recurrence score, 70-gene signature, ROR-P), ICR was the strongest predictive variable (p = 9.80E-04). ICR showed no prognostic value in the HR+/HER2- subtype, but prognostic value in the HER2+ and TN subtypes. Furthermore, in each molecular subtype and among the tumours defined as high risk by the three prognostic signatures, ICR4 patients had a 41-75% reduction in risk of relapse as compared with ICR1-3 patients. ICR added significant prognostic information to that provided by the clinico-genomic models in the overall population and in each molecular subtype. ICR4 was independently associated with achievement of pathological complete response to neoadjuvant chemotherapy (p = 2.97E-04).

Conclusion: ICR signature adds prognostic information to that of current proliferation-based signatures, with which it could be integrated to improve patients' stratification and guide adjuvant treatment.

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