Dataset Information

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.

SUBMITTER: Bertucci F

PROVIDER: S-EPMC6265245 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Bertucci François F Finetti Pascal P Simeone Ines I Hendrickx Wouter W Wang Ena E Marincola Francesco M FM Viens Patrice P Mamessier Emilie E Ceccarelli Michele M Birnbaum Daniel D Bedognetti Davide D

British journal of cancer 20181024 11

<h4>Background</h4>The immunologic constant of rejection (ICR) is a broad phenomenon of Th-1 immunity-mediated, tissue-specific destruction.<h4>Methods</h4>We tested the prognostic value of a 20-gene ICR expression signature in 8766 early breast cancers.<h4>Results</h4>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 ...[more]

PMID: 30353048

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Project description:BackgroundAnti-PD1/PDL1 immune checkpoint inhibitors (ICI) transformed the prognosis of patients with advanced non-small cell lung cancer (NSCLC). However, the response rate remains disappointing and toxicity may be life-threatening, making urgent identification of biomarkers predictive for efficacy. Immunologic Constant of Rejection signature (ICR) is a 20-gene expression signature of cytotoxic immune response with prognostic value in some solid cancers. Our objective was to assess its predictive value for benefit from anti-PD1/PDL1 in patients with advanced NSCLC.MethodsWe retrospectively profiled 44 primary tumors derived from NSCLC patients treated with ICI as single-agent in at least the second-line metastatic setting. Transcriptomic analysis was performed using the nCounter® analysis system and the PanCancer Immune Profiling Panel. We then pooled our data with clinico-biological data from four public gene expression data sets, leading to a total of 162 NSCLC patients treated with single-agent anti-PD1/PDL1. ICR was applied to all samples and correlation was searched between ICR classes and the Durable Clinical Benefit (DCB), defined as stable disease or objective response according to RECIST 1.1 for a minimum of 6 months after the start of ICI.ResultsThe DCB rate was 29%; 22% of samples were classified as ICR1, 30% ICR2, 22% ICR3, and 26% ICR4. These classes were not associated with the clinico-pathological variables, but showed enrichment from ICR1 to ICR4 in quantitative/qualitative markers of immune response. ICR2-4 class was associated with a 5.65-fold DCB rate when compared with ICR1 class. In multivariate analysis, ICR classification remained associated with DCB, independently from PDL1 expression and other predictive immune signatures. By contrast, it was not associated with disease-free survival in 556 NSCLC TCGA patients untreated with ICI.ConclusionThe 20-gene ICR signature was independently associated with benefit from anti-PD1/PDL1 ICI in patients with advanced NSCLC. Validation in larger retrospective and prospective series is warranted.

Project description:IntroductionThe overall survival rate is good for lymph-node-negative breast cancer patients, but they still suffer from serious over- and some undertreatments. Prognostic and predictive gene signatures for node-negative breast cancer have a high number of genes related to proliferation. The prognostic value of gene sets from commercial gene-expression assays were compared with proliferation markers.MethodsIllumina WG6 mRNA microarray analysis was used to examine 94 fresh-frozen tumour samples from node-negative breast cancer patients. The patients were divided into low- and high-risk groups for distant metastasis based on the MammaPrint-related genes, and into low-, intermediate- and high-risk groups based on the recurrence score algorithm with genes included in Oncotype DX. These data were then compared to proliferation status, as measured by the mitotic activity index, the expressions of phosphohistone H3 (PPH3), and Ki67.ResultsKaplan-Meier survival analysis for distant-metastasis-free survival revealed that patients with weak and strong PPH3 expressions had 14-year survival rates of 87% (n=45), and 65% (n=49, p=0.014), respectively. Analysis of the MammaPrint classification resulted in 14-year survival rates of 80% (n=45) and 71% (n=49, p=0.287) for patients with low and high risks of recurrence, respectively. The Oncotype DX categorization yielded 14-year survival rates of 83% (n=18), 79% (n=42) and 68% (n=34) for those in the low-, intermediate- and high-risk groups, respectively (p=0.52). Supervised hierarchical cluster analysis for distant-metastasis-free survival in the subgroup of patients with strong PPH3 expression revealed that the genes involved in Notch signalling and cell adhesion were expressed at higher levels in those patients with distant metastasis.ConclusionThis pilot study indicates that proliferation has greater prognostic value than the expressions of either MammaPrint- or Oncotype-DX-related genes. Furthermore, in the subgroup of patients with high proliferation, Notch signalling pathway genes appear to be expressed at higher levels in patients who develop distant metastasis.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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