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

被引：171

作者：

Issa-Nummer, Yasmin ^{[1
]}

Darb-Esfahani, Silvia ^{[2
]}

Loibl, Sibylle ^{[1
]}

Kunz, Georg ^{[3
]}

Nekljudova, Valentina ^{[1
]}

Schrader, Iris ^{[4
]}

Sinn, Bruno Valentin ^{[2
]}

Ulmer, Hans-Ullrich ^{[5
]}

Kronenwett, Ralf ^{[6
]}

Just, Marianne ^{[7
]}

Kuehn, Thorsten ^{[8
]}

Diebold, Kurt ^{[9
]}

Untch, Michael ^{[10
]}

Holms, Frank ^{[11
]}

Blohmer, Jens-Uwe ^{[12
]}

Habeck, Joerg-Olaf ^{[13
]}

Dietel, Manfred ^{[2
]}

Overkamp, Friedrich ^{[14
]}

Krabisch, Petra ^{[15
]}

von Minckwitz, Gunter ^{[1
,16
]}

Denkert, Carsten ^{[2
]}

机构：

[1] German Breast Grp, Neu Isenburg, Germany

[2] Charite, Inst Pathol, D-13353 Berlin, Germany

[3] St Johannes Hosp, Dept Gynecol & Obstet, Dortmund, Germany

[4] Frauenklin Henriettenstiftung, Hannover, Germany

[5] Stadt Klinikum Karlsruhe, Frauenklin, Karlsruhe, Germany

[6] Sividon Diagnost GmbH, Cologne, Germany

[7] Schwerpunktpraxis Bielefeld, Bielefeld, Germany

[8] Klinikum Esslingen, Klin Frauenheilkunde & Geburtshilfe, Esslingen, Germany

[9] Gemeinschaftspraxis Pathol Hamm, Hamm, Germany

[10] Helios Klinikum Berlin Buch, Breast Ctr, Berlin, Germany

[11] St Barbara Klin Hamm Heessen, Gynakol & Geburtshilfe, Hamm, Germany

[12] St Gertrauden Krankenhaus Berlin, Breast Ctr, Berlin, Germany

[13] Zentrum Histopathol Chemnitz, Chemnitz, Germany

[14] Oncol Nova GmbH Recklinghausen, Recklinghausen, Germany

[15] Klinikum Chemnitz, Breast Ctr, Chemnitz, Germany

[16] Univ Womens Hosp, Frankfurt, Germany

来源：

PLOS ONE | 2013年 / 8卷 / 12期

关键词：

REGULATORY T-CELLS; PREOPERATIVE CHEMOTHERAPY; PROGNOSTIC-FACTOR; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; B-CELLS; CYCLOPHOSPHAMIDE; LYMPHOCYTES; IMMUNOSURVEILLANCE; SURVIVAL;

D O I：

10.1371/journal.pone.0079775

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Introduction: 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. Patients and Methods: 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. Results: 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). Conclusion: 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.

引用

页数：7

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LYMPHOCYTE INFILTRATES AS A PROGNOSTIC VARIABLE IN FEMALE BREAST-CANCER [J].