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A 14-gene B-cell immune signature in early-stage triple-negative breast cancer (TNBC) : a pooled analysis of seven studies

Conte, Benedetta ; Brasó-Maristany, Fara ; Hernández, Adela Rodríguez ; Pascual, Tomás ; Villacampa, Guillermo ; Schettini, Francesco ; Vidal Losada, Maria J. ; Seguí, Elia ; Angelats, Laura and Garcia-Fructuoso, Isabel , et al. (2024) In EBioMedicine 102.
Abstract

Background: Early-stage triple-negative breast cancer (TNBC) displays clinical and biological diversity. From a biological standpoint, immune infiltration plays a crucial role in TNBC prognosis. Currently, there is a lack of genomic tools aiding in treatment decisions for TNBC. This study aims to assess the effectiveness of a B-cell/immunoglobulin signature (IGG) alone, or in combination with tumor burden, in predicting prognosis and treatment response in patients with TNBC. Methods: Genomic and clinical data were retrieved from 7 cohorts: SCAN-B (N = 874), BrighTNess (n = 482), CALGB-40603 (n = 389), METABRIC (n = 267), TCGA (n = 118), GSE58812 (n = 107), GSE21653 (n = 67). IGG and a risk score integrating IGG with tumor/nodal staging... (More)

Background: Early-stage triple-negative breast cancer (TNBC) displays clinical and biological diversity. From a biological standpoint, immune infiltration plays a crucial role in TNBC prognosis. Currently, there is a lack of genomic tools aiding in treatment decisions for TNBC. This study aims to assess the effectiveness of a B-cell/immunoglobulin signature (IGG) alone, or in combination with tumor burden, in predicting prognosis and treatment response in patients with TNBC. Methods: Genomic and clinical data were retrieved from 7 cohorts: SCAN-B (N = 874), BrighTNess (n = 482), CALGB-40603 (n = 389), METABRIC (n = 267), TCGA (n = 118), GSE58812 (n = 107), GSE21653 (n = 67). IGG and a risk score integrating IGG with tumor/nodal staging (IGG-Clin) were assessed for event-free survival (EFS) and overall survival (OS) in each cohort. Random effects model was used to derive pooled effect sizes. Association of IGG with pathological complete response (pCR) was assessed in CALGB-40603 and BrighTNess. Immune significance of IGG was estimated through CIBERSORTx and EcoTyper. Findings: IGG was associated with improved EFS (pooled HR = 0.77, [95% CI = 0.70–0.85], I2 = 18%) and OS (pooled HR = 0.79, [0.73–0.85], I2 = 0%) across cohorts, and was predictive of pCR in CALGB-40603 (OR 1.25, [1.10–1.50]) and BrighTNess (OR 1.57 [1.25–1.98]). IGG-Clin was predictive of recurrence (pooled HR = 2.11, [1.75–2.55], I2 = 0%) and death (pooled HR = 1.99, 95% [0.84–4.73], I2 = 79%) across cohorts. IGG was associated with adaptive immune response at CIBERSORTx and EcoTyper analysis. Interpretation: IGG is linked to improved prognosis and pCR in early-stage TNBC. The integration of IGG alongside tumor and nodal staging holds promise as an approach to identify patients benefitting from intensified or de-intensified treatments. Funding: This study received funding from: Associació Beca Marta Santamaria, European Union's Horizon 2020 research and innovation and Marie Skłodowska–Curie Actions programs, Fundación FERO, Fundación CRIS contra el cáncer, Agència de Gestó d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, Fundación Contigo, Asociación Cáncer de Mama Metastásico IV, Breast Cancer Research Foundation, RESCUER, Fundación científica AECC and FSEOM.

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publication status
published
subject
keywords
B-cell/immunoglobulin signature (IGG), Event-free survival (EFS), Gene expression, Overall survival (OS), Pathological complete response (pCR), Predictive biomarkers, Prognostic biomarkers, Triple-negative breast cancer (TNBC)
in
EBioMedicine
volume
102
article number
105043
publisher
Elsevier
external identifiers
  • pmid:38447275
  • scopus:85186640223
ISSN
2352-3964
DOI
10.1016/j.ebiom.2024.105043
language
English
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yes
id
bf6692c0-9c47-44dc-b6e4-3ee96d75a955
date added to LUP
2024-03-14 11:50:49
date last changed
2024-04-25 08:28:26
@article{bf6692c0-9c47-44dc-b6e4-3ee96d75a955,
  abstract     = {{<p>Background: Early-stage triple-negative breast cancer (TNBC) displays clinical and biological diversity. From a biological standpoint, immune infiltration plays a crucial role in TNBC prognosis. Currently, there is a lack of genomic tools aiding in treatment decisions for TNBC. This study aims to assess the effectiveness of a B-cell/immunoglobulin signature (IGG) alone, or in combination with tumor burden, in predicting prognosis and treatment response in patients with TNBC. Methods: Genomic and clinical data were retrieved from 7 cohorts: SCAN-B (N = 874), BrighTNess (n = 482), CALGB-40603 (n = 389), METABRIC (n = 267), TCGA (n = 118), GSE58812 (n = 107), GSE21653 (n = 67). IGG and a risk score integrating IGG with tumor/nodal staging (IGG-Clin) were assessed for event-free survival (EFS) and overall survival (OS) in each cohort. Random effects model was used to derive pooled effect sizes. Association of IGG with pathological complete response (pCR) was assessed in CALGB-40603 and BrighTNess. Immune significance of IGG was estimated through CIBERSORTx and EcoTyper. Findings: IGG was associated with improved EFS (pooled HR = 0.77, [95% CI = 0.70–0.85], I<sup>2</sup> = 18%) and OS (pooled HR = 0.79, [0.73–0.85], I<sup>2</sup> = 0%) across cohorts, and was predictive of pCR in CALGB-40603 (OR 1.25, [1.10–1.50]) and BrighTNess (OR 1.57 [1.25–1.98]). IGG-Clin was predictive of recurrence (pooled HR = 2.11, [1.75–2.55], I<sup>2</sup> = 0%) and death (pooled HR = 1.99, 95% [0.84–4.73], I<sup>2</sup> = 79%) across cohorts. IGG was associated with adaptive immune response at CIBERSORTx and EcoTyper analysis. Interpretation: IGG is linked to improved prognosis and pCR in early-stage TNBC. The integration of IGG alongside tumor and nodal staging holds promise as an approach to identify patients benefitting from intensified or de-intensified treatments. Funding: This study received funding from: Associació Beca Marta Santamaria, European Union's Horizon 2020 research and innovation and Marie Skłodowska–Curie Actions programs, Fundación FERO, Fundación CRIS contra el cáncer, Agència de Gestó d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, Fundación Contigo, Asociación Cáncer de Mama Metastásico IV, Breast Cancer Research Foundation, RESCUER, Fundación científica AECC and FSEOM.</p>}},
  author       = {{Conte, Benedetta and Brasó-Maristany, Fara and Hernández, Adela Rodríguez and Pascual, Tomás and Villacampa, Guillermo and Schettini, Francesco and Vidal Losada, Maria J. and Seguí, Elia and Angelats, Laura and Garcia-Fructuoso, Isabel and Gómez-Bravo, Raquel and Lorman-Carbó, Natàlia and Paré, Laia and Marín-Aguilera, Mercedes and Martínez-Sáez, Olga and Adamo, Barbara and Sanfeliu, Esther and Fratini, Beatrice and Falato, Claudette and Chic, Núria and Vivancos, Ana and Villagrasa, Patricia and Staaf, Johan and Parker, Joel S. and Perou, Charles M. and Prat, Aleix}},
  issn         = {{2352-3964}},
  keywords     = {{B-cell/immunoglobulin signature (IGG); Event-free survival (EFS); Gene expression; Overall survival (OS); Pathological complete response (pCR); Predictive biomarkers; Prognostic biomarkers; Triple-negative breast cancer (TNBC)}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{EBioMedicine}},
  title        = {{A 14-gene B-cell immune signature in early-stage triple-negative breast cancer (TNBC) : a pooled analysis of seven studies}},
  url          = {{http://dx.doi.org/10.1016/j.ebiom.2024.105043}},
  doi          = {{10.1016/j.ebiom.2024.105043}},
  volume       = {{102}},
  year         = {{2024}},
}