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
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
收藏
页码:5747 / 5754
页数:8
相关论文
共 32 条
[1]   Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199 [J].
Adams, Sylvia ;
Gray, Robert J. ;
Demaria, Sandra ;
Goldstein, Lori ;
Perez, Edith A. ;
Shulman, Lawrence N. ;
Martino, Silvana ;
Wang, Molin ;
Jones, Vicky E. ;
Saphner, Thomas J. ;
Wolff, Antonio C. ;
Wood, William C. ;
Davidson, Nancy E. ;
Sledge, George W. ;
Sparano, Joseph A. ;
Badve, Sunil S. .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :2959-+
[2]   Phase II study of weekly intravenous recombinant humanized Anti-p185(HER2) monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast [J].
Baselga, J ;
Tripathy, D ;
Mendelsohn, J ;
Baughman, S ;
Benz, CC ;
Dantis, L ;
Sklarin, NT ;
Seidman, AD ;
Hudis, CA ;
Moore, J ;
Rosen, PP ;
Twaddell, T ;
Henderson, IC ;
Norton, L .
JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (03) :737-744
[3]   The immune system and response to HER2-targeted treatment in breast cancer [J].
Bianchini, Giampaolo ;
Gianni, Luca .
LANCET ONCOLOGY, 2014, 15 (02) :E58-E68
[4]   Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib [J].
Carey, Lisa A. ;
Berry, Donald A. ;
Cirrincione, Constance T. ;
Barry, William T. ;
Pitcher, Brandelyn N. ;
Harris, Lyndsay N. ;
Ollila, David W. ;
Krop, Ian E. ;
Henry, Norah Lynn ;
Weckstein, Douglas J. ;
Anders, Carey K. ;
Singh, Baljit ;
Hoadley, Katherine A. ;
Iglesia, Michael ;
Cheang, Maggie Chon U. ;
Perou, Charles M. ;
Winer, Eric P. ;
Hudis, Clifford A. .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (06) :542-+
[5]   Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets [J].
Clynes, RA ;
Towers, TL ;
Presta, LG ;
Ravetch, JV .
NATURE MEDICINE, 2000, 6 (04) :443-446
[6]   The immunogenicity of breast cancer-molecular subtypes matter [J].
Denkert, C. .
ANNALS OF ONCOLOGY, 2014, 25 (08) :1453-1455
[7]   Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2-Positive and Triple-Negative Primary Breast Cancers [J].
Denkert, Carsten ;
von Minckwitz, Gunter ;
Brase, Jan C. ;
Sinn, Bruno V. ;
Gade, Stephan ;
Kronenwett, Ralf ;
Pfitzner, Berit M. ;
Salat, Christoph ;
Loi, Sherene ;
Schmitt, Wolfgang D. ;
Schem, Christian ;
Fisch, Karin ;
Darb-Esfahani, Silvia ;
Mehta, Keyur ;
Sotiriou, Christos ;
Wienert, Stephan ;
Klare, Peter ;
Andre, Fabrice ;
Klauschen, Frederick ;
Blohmer, Jens-Uwe ;
Krappmann, Kristin ;
Schmidt, Marcus ;
Tesch, Hans ;
Kuemmel, Sherko ;
Sinn, Peter ;
Jackisch, Christian ;
Dietel, Manfred ;
Reimer, Toralf ;
Untch, Michael ;
Loibl, Sibylle .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (09) :983-991
[8]   Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer [J].
Denkert, Carsten ;
Loibl, Sibylle ;
Noske, Aurelia ;
Roller, Marc ;
Mueller, Berit Maria ;
Komor, Martina ;
Budczies, Jan ;
Darb-Esfahani, Silvia ;
Kronenwett, Ralf ;
Hanusch, Claus ;
von Toerne, Christian ;
Weichert, Wilko ;
Engels, Knut ;
Solbach, Christine ;
Schrader, Iris ;
Dietel, Manfred ;
von Minckwitz, Gunter .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (01) :105-113
[9]   Lapatinib plus capecitabine for HER2-positive advanced breast cancer [J].
Geyer, Charles E. ;
Forster, John ;
Lindquist, Deborah ;
Chan, Stephen ;
Romieu, C. Gilles ;
Pienkowski, Tadeusz ;
Jagiello-Gruszfeld, Agnieszka ;
Crown, John ;
Chan, Arlene ;
Kaufman, Bella ;
Skarlos, Dimosthenis ;
Campone, Mario ;
Davidson, Neville ;
Berger, Mark ;
Oliva, Cristina ;
Rubin, Stephen D. ;
Stein, Steven ;
Cameron, David .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (26) :2733-2743
[10]   Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial [J].
Gianni, Luca ;
Pienkowski, Tadeusz ;
Im, Young-Hyuck ;
Roman, Laslo ;
Tseng, Ling-Ming ;
Liu, Mei-Ching ;
Lluch, Ana ;
Staroslawska, Elzbieta ;
de la Haba-Rodriguez, Juan ;
Im, Seock-Ah ;
Pedrini, Jose Luiz ;
Poirier, Brigitte ;
Morandi, Paolo ;
Semiglazov, Vladimir ;
Srimuninnimit, Vichien ;
Bianchi, Giulia ;
Szado, Tania ;
Ratnayake, Jayantha ;
Ross, Graham ;
Valagussa, Pinuccia .
LANCET ONCOLOGY, 2012, 13 (01) :25-32