The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

作者：Marcus Schmidt, Daniel Böhm, Christian von Törne, Eric Steiner, Alexander Puhl, Henryk Pilch, Hans‐Anton Lehr, Jan G. Hengstler, H. Kölbl, Mathias Gehrmann · 发表于：Cancer Research · 年份：2008 · DOI：10.1158/0008-5472.can-07-5206 · 被引用次数：860 · 研究领域：Breast Cancer Treatment Studies、Cancer Cells and Metastasis、Cancer Immunotherapy and Biomarkers

Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation-associated genes. In multivariate Cox regression analysis, the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort [hazard ratio (HR), 2.20; 95% confidence interval (95% CI), 1.40-3.46]. The B-cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR, 0.66; 95% CI, 0.46-0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high-grade tumors (n = 286; HR, 0.78; 95% CI, 0.62-0.98) and a second validation cohort enriched for young...