Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer

被引：161

作者：

Heppner, Barbara Ingold ^{[1
]}

Untch, Michael ^{[2
]}

Denkert, Carsten ^{[1
,3
]}

Pfitzner, Berit M. ^{[1
]}

Lederer, Bianca ^{[4
]}

Schmitt, Wolfgang ^{[1
]}

Eidtmann, Holger ^{[5
]}

Fasching, Peter A. ^{[6
]}

Tesch, Hans ^{[7
]}

Solbach, Christine ^{[8
]}

Rezai, Mahdi ^{[9
]}

Zahm, Dirk M. ^{[10
]}

Holms, Frank ^{[11
]}

Glados, Manfred ^{[12
]}

Krabisch, Petra ^{[13
]}

Heck, Esther ^{[14
]}

Ober, Angelika ^{[15
]}

Lorenz, Petra ^{[16
]}

Diebold, Kurt ^{[17
]}

Habeck, Jorg-Olaf ^{[18
]}

Loib, Sibylle ^{[4
]}

机构：

[1] Charite, Inst Pathol, Berlin, Germany

[2] Helios Klinikum Berlin Buch, Klin Gynakol & Geburtshilfe, Berlin, Germany

[3] German Canc Consortium DKTK, Berlin, Germany

[4] German Breast Grp GBG Forsch GmbH, Neu Isenburg, Germany

[5] UK SH, Klin Gynakol & Geburtshilfe, Kiel, Germany

[6] UK Erlangen, Frauenklin, Erlangen, Germany

[7] Onkol Bethanien, Frankfurt, Germany

[8] UKF, Klin Frauenheilkunde & Geburtshilfe, Frankfurt, Germany

[9] Luisenkrankenhaus Dusseldorf, MCD, Dusseldorf, Germany

[10] SRH Waldklinikum Gera, Brustzentrum, Gera, Germany

[11] Brustzentrum, St Barbara Klin, Hamm Hessen, Germany

[12] Onkol Gemeinschaftspraxis, Coesfeld, Germany

[13] Klinikum Chemnitz, Klin Frauenheilkunde & Geburtshilfe, Chemnitz, Germany

[14] Johanna Etienne Krankenhaus, Gynakol, Neuss, Germany

[15] St Vincenz Hosp, Frauenklin, Limburg, Germany

[16] SRH Waldklinikum Gera, Pathol, Gera, Germany

[17] Inst Pathol, St Barbara Klin, Hamm Heessen, Germany

[18] Zentrum Histopathol, Chemnitz, Germany

来源：

CLINICAL CANCER RESEARCH | 2016年 / 22卷 / 23期

关键词：

TAXANE-BASED CHEMOTHERAPY; FREE SURVIVAL; OPEN-LABEL; TRASTUZUMAB; LAPATINIB; RECEPTOR; THERAPY; CAPECITABINE; TRIAL; RECOMMENDATIONS;

D O I：

10.1158/1078-0432.CCR-15-2338

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: We elucidated the value of tumor-infiltrating lymphocytes (TIL) as an independent predictor for pathologic complete response (pCR) rate and as a prognostic marker for disease-free survival (DFS) in patients with HER2-positive breast cancer in the neoadjuvant setting. Experimental Design: We evaluated stromal TILs in 498 HER2-positive breast cancer samples of the neoadjuvant GeparQuattro (G4) and GeparQuinto (G5) trials. Levels of TILs were determined as a continuous parameter per 10% increase and as lymphocyte-predominant breast cancer (LPBC; >= 60% TILs), and correlated with pCR rate and DFS. Results: In the complete cohort, HER2-positive LPBC cases had a significantly increased pCR rates compared with non-LPBC types. They were significant predictors for pCR in univariate (10% TILs: OR 1.12, P = 0.002; LPBC: OR 2.02, P = 0.002) and multivariate analyses (10% TILs: OR 1.1, P = 0.014; LPBC: OR 1.87, P = 0.009). This effect was also detectable in the trastuzumab-treated (10% TILs: OR 1.12, P = 0.018; LPBC: OR 2.08, P = 0.013) but not in the lapatinib-treated subgroup. We identified a low-risk (pCR/LPBC) and a high-risk group (no pCR/no LPBC) regarding DFS. In triple-positive breast cancer, TILs are of more prognostic relevance than pCR. Conclusions: We could demonstrate the predictive and prognostic impact of TILs in HER2-positive breast cancer in the neoadjuvant setting. In combination with pCR rate, TILs may help to stratify prognostic subgroups, thereby guiding future therapy decisions. (C) 2016 AACR.

引用

页码：5747 / 5754

页数：8

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