Abstract
Abstract Background: The prognostic significance of CD8 positive cytotoxic lymphocytes in breast cancer is well accepted. However, the role of CD4 positive lymphocytes is ambiguous. We examined the prognostic relevance of CD4 positive tumor-infiltrating lymphocytes in previously published node-negative breast cancer cohorts using RNA expression. Methods: Microarray based gene-expression data for CD4 (203547_at) were analyzed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CD4 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes (ER+/HER2−, ER−/HER2−, HER2+). Independent prognostic relevance was analyzed using multivariate Cox regression. Results: Higher RNA expression of CD4 was related to better MFS in a meta-analysis of the whole cohort (HR 0.66, 95% CI 0.49–0.90, p = 0.0074). Prognostic significance was most pronounced in the HER2+ positive molecular subtype (HR 0.32, 95% CI 0.14–0.75, p = 0.0091) as compared to ER+/HER2− (HR 0.62, 95% CI 0.29–1.32, P>0.05) and ER−/HER2− (HR 0.61, 95% CI 0.28–1.35, P>0.05) carcinomas of the breast. CD4 showed independent prognostic significance (HR 0.60, 95% CI 0.37–0.96, p = 0.032) in multivariate analysis. In addition to CD4, only histological grade of differentiation (HR 2.43, 95% CI 1.50–3.94, P < 0.001) and tumor size (HR 1.87, 95% CI 1.19–2.94, p = 0.007), but not age, HER2 status or hormone receptor status retained an independent prognostic association with MFS. Conclusion: CD4 positive tumor-infiltrating lymphocytes have independent prognostic significance in node-negative breast cancer. A higher expression is associated with improved outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-13.
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