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

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), CALGB40603 (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 deintensified treatments. Agencia de Gesto d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, Fundacion Contigo, Asociacion Cancer de Mama Metastasico IV, Breast Cancer Research Foundation, RESCUER, Fundacion cientifica AECC and FSEOM. Copyright (c) 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).