Journal Article

Prospective Validation of Immunological Infiltrate for Prediction of Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer – A Substudy of the Neoadjuvant GeparQuinto Trial

Just, Marianne, Blohmer, Jens-Uwe, Denkert, Carsten, Dietel, Manfred, Sinn, Bruno Valentin, Kühn, Thorsten, Schrader, Iris, Ulmer, Hans-Ullrich, Holms, Frank, Krabisch, Petra, Loibl, Sibylle, Kunz, Georg, Issa-Nummer, Yasmin, Nekljudova, Valentina, Habeck, Jörg-Olaf, Overkamp, Friedrich, von Minckwitz, Gunter, Kronenwett, Ralf, Untch, Michael, Diebold, Kurt, Darb-Esfahani, Silvia

2013

Overview

We have recently described an increased lymphocytic infiltration rate in breast carcinoma tissue is a significant response predictor for anthracycline/taxane-based neoadjuvant chemotherapy (NACT). The aim of this study was to prospectively validate the tumor-associated lymphocyte infiltrate as predictive marker for response to anthracycline/taxane-based NACT. The immunological infiltrate was prospectively evaluated in a total of 313 core biopsies from HER2 negative patients of the multicenter PREDICT study, a substudy of the neoadjuvant GeparQuinto study. Intratumoral lymphocytes (iTuLy), stromal lymphocytes (strLy) as well as lymphocyte-predominant breast cancer (LPBC) were evaluated by histopathological assessment. Pathological complete response (pCR) rates were analyzed and compared between the defined subgroups using the exact test of Fisher. Patients with lymphocyte-predominant breast cancer (LPBC) had a significantly increased pCR rate of 36.6%, compared to non-LPBC patients (14.3%, p<0.001). LPBC and stromal lymphocytes were significantly independent predictors for pCR in multivariate analysis (LPBC: OR 2.7, p = 0.003, strLy: OR 1.2, p = 0.01). The amount of intratumoral lymphocytes was significantly predictive for pCR in univariate (OR 1.2, p = 0.01) but not in multivariate logistic regression analysis (OR 1.2, p = 0.11). Confirming previous investigations of our group, we have prospectively validated in an independent cohort that an increased immunological infiltrate in breast tumor tissue is predictive for response to anthracycline/taxane-based NACT. Patients with LPBC and increased stromal lymphocyte infiltration have significantly increased pCR rates. The lymphocytic infiltrate is a promising additional parameter for histopathological evaluation of breast cancer core biopsies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Analysis / Anthracycline / Anthracyclines - administration & dosage / Antigens / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Biopsy / Breast cancer / Breast carcinoma / Breast Neoplasms - drug therapy / Breast Neoplasms - immunology / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Bridged-Ring Compounds - administration & dosage / Cancer / Cancer therapies / Care and treatment / Chemotherapy / ErbB-2 protein / Female / Humans / Immune system / Immunology / Infiltration / Infiltration (Hydrology) / Infiltration rate / Infiltration rates / Lymphocytes / Lymphocytes - immunology / Lymphocytes - pathology / Metastases / Middle Aged / Multivariate analysis / Neoadjuvant Therapy / Pathology / Patients / Predictions / Prospective Studies / Receptor, ErbB-2 / Regression analysis / Subgroups / Taxane / Taxanes / Taxoids - administration & dosage / Tumors