The immunologic constant of rejection classification refines the prognostic value of conventional prognostic signatures in breast cancer

François Bertucci, Pascal Finetti, Ines Simeone, Wouter R. Hendrickx, Ena Wang, Francesco M. Marincola, Patrice Viens, Emilie Mamessier, Michele Ceccarelli, Daniel Birnbaum, Davide Bedognetti

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
JournalBritish Journal of Cancer
DOIs
Publication statusAccepted/In press - 1 Jan 2018

Fingerprint

Breast Neoplasms
Risk Reduction Behavior
Recurrence
Genes
Rejection (Psychology)
Immunity
Neoplasms
Multivariate Analysis
Drug Therapy
Population
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The immunologic constant of rejection classification refines the prognostic value of conventional prognostic signatures in breast cancer. / Bertucci, François; Finetti, Pascal; Simeone, Ines; Hendrickx, Wouter R.; Wang, Ena; Marincola, Francesco M.; Viens, Patrice; Mamessier, Emilie; Ceccarelli, Michele; Birnbaum, Daniel; Bedognetti, Davide.

In: British Journal of Cancer, 01.01.2018.

Research output: Contribution to journalArticle

Bertucci, François ; Finetti, Pascal ; Simeone, Ines ; Hendrickx, Wouter R. ; Wang, Ena ; Marincola, Francesco M. ; Viens, Patrice ; Mamessier, Emilie ; Ceccarelli, Michele ; Birnbaum, Daniel ; Bedognetti, Davide. / The immunologic constant of rejection classification refines the prognostic value of conventional prognostic signatures in breast cancer. In: British Journal of Cancer. 2018.
@article{157fddeb2fa64117830345515aee1539,
title = "The immunologic constant of rejection classification refines the prognostic value of conventional prognostic signatures in breast cancer",
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.",
author = "Fran{\cc}ois Bertucci and Pascal Finetti and Ines Simeone and Hendrickx, {Wouter R.} and Ena Wang and Marincola, {Francesco M.} and Patrice Viens and Emilie Mamessier and Michele Ceccarelli and Daniel Birnbaum and Davide Bedognetti",
year = "2018",
month = "1",
day = "1",
doi = "10.1038/s41416-018-0309-1",
language = "English",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - The immunologic constant of rejection classification refines the prognostic value of conventional prognostic signatures in breast cancer

AU - Bertucci, François

AU - Finetti, Pascal

AU - Simeone, Ines

AU - Hendrickx, Wouter R.

AU - Wang, Ena

AU - Marincola, Francesco M.

AU - Viens, Patrice

AU - Mamessier, Emilie

AU - Ceccarelli, Michele

AU - Birnbaum, Daniel

AU - Bedognetti, Davide

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85055566075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055566075&partnerID=8YFLogxK

U2 - 10.1038/s41416-018-0309-1

DO - 10.1038/s41416-018-0309-1

M3 - Article

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

ER -