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

Benedetta Conte ¹, Fara Brasó-Maristany ², Adela Rodríguez Hernández ¹

¹Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Cancer Institute and Blood Diseases, Hospital Clinic de Barcelona, Barcelona, Spain.
²Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Cancer Institute and Blood Diseases, Hospital Clinic de Barcelona, Barcelona, Spain; Reveal Genomics, Barcelona, Spain.
³Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Cancer Institute and Blood Diseases, Hospital Clinic de Barcelona, Barcelona, Spain; SOLTI Cooperative Group, Barcelona, Spain.
⁴Reveal Genomics, Barcelona, Spain; SOLTI Cooperative Group, Barcelona, Spain; Oncology Data Science, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
⁵Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Cancer Institute and Blood Diseases, Hospital Clinic de Barcelona, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain.
⁶Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Cancer Institute and Blood Diseases, Hospital Clinic de Barcelona, Barcelona, Spain; SOLTI Cooperative Group, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain; Institute of Oncology (IOB)-Hospital QuirónSalud, Barcelona, Spain.
⁷Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
⁸Reveal Genomics, Barcelona, Spain.
⁹Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Pathology Department, Hospital Clinic of Barcelona, Barcelona, Spain.
¹⁰Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; SOLTI Cooperative Group, Barcelona, Spain.
¹¹Reveal Genomics, Barcelona, Spain; Vall d'Hebron Institute of Oncology (VHIO), Cancer Genomics Group, Barcelona, Spain.
¹²Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Sweden.
¹³Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
¹⁴Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
¹⁵Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Cancer Institute and Blood Diseases, Hospital Clinic de Barcelona, Barcelona, Spain; Reveal Genomics, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain; Institute of Oncology (IOB)-Hospital QuirónSalud, Barcelona, Spain.

⁰Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Cancer Institute and Blood Diseases, Hospital Clinic de Barcelona, Barcelona, Spain.

Ebiomedicine +

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March 6, 2024

View abstract on PubMed

Summary

A B-cell/immunoglobulin signature (IGG) improves prognosis and predicts treatment response in early-stage triple-negative breast cancer (TNBC). Integrating IGG with clinical staging may guide personalized treatment strategies for TNBC patients.

Area Of Science

Oncology
Genomics
Immunology

Background

Early-stage triple-negative breast cancer (TNBC) exhibits significant clinical and biological heterogeneity.
Immune cell infiltration is a critical factor influencing TNBC patient outcomes.
Genomic tools for guiding TNBC treatment decisions are currently limited.

Purpose Of The Study

To evaluate the prognostic and predictive value of a B-cell/immunoglobulin signature (IGG) in early-stage TNBC.
To assess the combined effectiveness of IGG and tumor burden (IGG-Clin) in predicting patient outcomes.
To explore the association of IGG with pathological complete response (pCR) and immune response in TNBC.

Main Methods

Analysis of genomic and clinical data from seven independent patient cohorts (N=2456).
Assessment of IGG and IGG-Clin for event-free survival (EFS) and overall survival (OS) using a random effects model.
Evaluation of IGG association with pCR in two cohorts and immune significance via CIBERSORTx and EcoTyper.

Main Results

IGG was significantly associated with improved EFS and OS across all cohorts.
IGG predicted pathological complete response (pCR) in the CALGB-40603 and BrighTNess cohorts.
IGG-Clin demonstrated predictive value for recurrence and death, and IGG correlated with adaptive immune response.

Conclusions

The B-cell/immunoglobulin signature (IGG) is linked to better prognosis and pCR in early-stage TNBC.
Combining IGG with tumor and nodal staging (IGG-Clin) shows potential for identifying patients who may benefit from tailored treatment intensification or de-intensification.

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)