Abstract

BackgroundEarly-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. MethodsGenomic 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. ResultsIGG 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. InterpretationIGG 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: European Union’s Horizon 2020 research and innovation and Marie Skłodowska–Curie Actions programs, Fundación CRIS contra el cáncer, Agència de Gestó d'Ajuts Universitaris i de Recerca, Fundación Fero, Instituto de Salud Carlos III, Asociación Cáncer de Mama Metastásico IV, Breast Cancer Research Foundation, RESCUER, Fundación científica AECC and FSEOM.

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