Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer

作者：Carsten Denkert, Sibylle Loibl, Aurelia Noske, Marc Roller, Berit Müller, Martina Komor, Jan Budczies, Silvia Darb‐Esfahani, Ralf Kronenwett, Claus Hanusch, Christian von Törne, Wilko Weichert, Knut Engels, Christine Solbach, Iris Schrader, Manfred Dietel, Gϋnter von Minckwitz · 发表于：Journal of Clinical Oncology · 年份：2009 · DOI：10.1200/jco.2009.23.7370 · 被引用次数：1802 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer Cells and Metastasis、Immunotherapy and Immune Responses

PURPOSE Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. METHODS We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR. CONCLUSION The presence of tumor-associa...