Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy

被引：151

作者：

Luen, S. J. ^{[1
]}

Salgado, R. ^{[1
,2
]}

Dieci, M. V. ^{[3
,4
]}

Vingiani, A. ^{[5
]}

Curigliano, G. ^{[5
,6
]}

Gould, R. E. ^{[7
]}

Castaneda, C. ^{[8
]}

D'Alfonso, T. ^{[9
]}

Sanchez, J. ^{[8
]}

Cheng, E. ^{[10
]}

Andreopoulou, E. ^{[10
]}

Castillo, M. ^{[8
]}

Adams, S. ^{[11
]}

Demaria, S. ^{[10
]}

Symmans, W. F. ^{[7
]}

Michiels, S. ^{[12
]}

Loi, S. ^{[1
]}

机构：

[1] Univ Melbourne, Peter MacCallum Canc Ctr, 305 Grattan St, Melbourne, Vic 3000, Australia

[2] GZA ZNA Hosp, Dept Pathol, Antwerp, Belgium

[3] Univ Padua, Padua, Italy

[4] IRCCS, Veneto Inst Oncol IOV, Padua, Italy

[5] IRCCS, European Inst Oncol, Milan, Italy

[6] Univ Milan, Milan, Italy

[7] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[8] Inst Nacl Enfermedades Neoplas, Lima, Peru

[9] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[10] Weill Cornell Med, Dept Radiat Oncol & Pathol & Lab Med, New York, NY USA

[11] NYU, Sch Med, New York, NY USA

[12] Univ Paris Saclay, Univ Paris Sud, Gustave Roussy, Serv Biostat & Epidemiol, Villejuif, France

来源：

ANNALS OF ONCOLOGY | 2019年 / 30卷 / 02期

关键词：

TILs; TNBC; RCB; prognosis; neoadjuvant;

D O I：

10.1093/annonc/mdy547

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC. Patients and methods: We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs. Results: A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10-40). There was a positive correlation between RD TIL levels and CD8thorn T-cell density (q = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79-0.92; P< 0.001), and improved OS (HR: 0.87; 95% CI 0.80-0.94; P< 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P< 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (PInt = 0.003) and OS (PInt = 0.008) with a greater magnitude of positive effect observed for RCB class II than class III. Conclusions: TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.

引用

页码：236 / 242

页数：7

共 14 条

[1] Prediction of survival after neoadjuvant chemotherapy for breast cancer by evaluation of tumor-infiltrating lymphocytes and residual cancer burden [J].

Asano, Yuka ;

Kashiwagi, Shinichiro ;

Goto, Wataru ;

Takada, Koji ;

Takahashi, Katsuyuki ;

Hatano, Takaharu ;

Noda, Satoru ;

Takashima, Tsutomu ;

Onoda, Naoyoshi ;

Tomita, Shuhei ;

Motomura, Hisashi ;

Ohsawa, Masahiko ;

Hirakawa, Kosei ;

Ohira, Masaichi .

BMC CANCER, 2017, 17

[2] Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [J].

Cortazar, Patricia ;

Zhang, Lijun ;

Untch, Michael ;

Mehta, Keyur ;

Costantino, Joseph P. ;

Wolmark, Norman ;

Bonnefoi, Herve ;

Cameron, David ;

Gianni, Luca ;

Valagussa, Pinuccia ;

Swain, Sandra M. ;

Prowell, Tatiana ;

Loibl, Sibylle ;

Wickerham, D. Lawrence ;

Bogaerts, Jan ;

Baselga, Jose ;

Perou, Charles ;

Blumenthal, Gideon ;

Blohmer, Jens ;

Mamounas, Eleftherios P. ;

Bergh, Jonas ;

Semiglazov, Vladimir ;

Justice, Robert ;

Eidtmann, Holger ;

Paik, Soonmyung ;

Piccart, Martine ;

Sridhara, Rajeshwari ;

Fasching, Peter A. ;

Slaets, Leen ;

Tang, Shenghui ;

Gerber, Bernd ;

Geyer, Charles E., Jr. ;

Pazdur, Richard ;

Ditsch, Nina ;

Rastogi, Priya ;

Eiermann, Wolfgang ;

von Minckwitz, Gunter .

LANCET, 2014, 384 (9938) :164-172

[3] A gene signature to predict high tumor-infiltrating lymphocytes after neoadjuvant chemotherapy and outcome in patients with triple-negative breast cancer [J].

Criscitiello, C. ;

Bayar, M. A. ;

Curigliano, G. ;

Symmans, F. W. ;

Desmedt, C. ;

Bonnefoi, H. ;

Sinn, B. ;

Pruneri, G. ;

Vicier, C. ;

Pierga, J. Y. ;

Denkert, C. ;

Loibl, S. ;

Sotiriou, C. ;

Michiels, S. ;

Andre, F. .

ANNALS OF ONCOLOGY, 2018, 29 (01) :162-169

[4] Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy [J].

Denkert, Carsten ;

von Minckwitz, Gunter ;

Darb-Esfahani, Silvia ;

Lederer, Bianca ;

Heppner, Barbara I. ;

Weber, Karsten E. ;

Budczies, Jan ;

Huober, Jens ;

Klauschen, Frederick ;

Furlanetto, Jenny ;

Schmitt, Wolfgang D. ;

Blohmer, Jens-Uwe ;

Karn, Thomas ;

Pfitzner, Berit M. ;

Kuemmel, Sherko ;

Engels, Knut ;

Schneeweiss, Andreas ;

Hartmann, Arndt ;

Noske, Aurelia ;

Fasching, Peter A. ;

Jackisch, Christian ;

van Mackelenbergh, Marion ;

Sinn, Peter ;

Schem, Christian ;

Hanusch, Claus ;

Untch, Michael ;

Loibl, Sibylle .

LANCET ONCOLOGY, 2018, 19 (01) :40-50

[5] Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study [J].

Dieci, M. V. ;

Criscitiello, C. ;

Goubar, A. ;

Viale, G. ;

Conte, P. ;

Guarneri, V. ;

Ficarra, G. ;

Mathieu, M. C. ;

Delaloge, S. ;

Curigliano, G. ;

Andre, F. .

ANNALS OF ONCOLOGY, 2014, 25 (03) :611-618

[6] Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer [J].

Dieci, Maria Vittoria ;

Radosevic-Robin, Nina ;

Fineberg, Susan ;

van den Eynden, Gert ;

Ternes, Nils ;

Penault-Llorca, Frederique ;

Pruneri, Giancarlo ;

D'Alfonso, Timothy M. ;

Demaria, Sandra ;

Castaneda, Carlos ;

Sanchez, Joselyn ;

Badve, Sunil ;

Michiels, Stefan ;

Bossuyt, Veerle ;

Rojo, Federico ;

Singh, Baljit ;

Nielsen, Torsten ;

Viale, Giuseppe ;

Kim, Seong-Rim ;

Hewitt, Stephen ;

Wienert, Stephan ;

Loibl, Sybille ;

Rimm, David ;

Symmans, Fraser ;

Denkert, Carsten ;

Adams, Sylvia ;

Loi, Sherene ;

Salgado, Roberto .

SEMINARS IN CANCER BIOLOGY, 2018, 52 :16-25

[7] T-cell invigoration to tumour burden ratio associated with anti-PD-1 response [J].

Huang, Alexander C. ;

Postow, Michael A. ;

Orlowski, Robert J. ;

Mick, Rosemarie ;

Bengsch, Bertram ;

Manne, Sasikanth ;

Xu, Wei ;

Harmon, Shannon ;

Giles, Josephine R. ;

Wenz, Brandon ;

Adamow, Matthew ;

Kuk, Deborah ;

Panageas, Katherine S. ;

Carrera, Cristina ;

Wong, Phillip ;

Quagliarello, Felix ;

Wubbenhorst, Bradley ;

D'Andrea, Kurt ;

Pauken, Kristen E. ;

Herati, Ramin S. ;

Staupe, Ryan P. ;

Schenkel, Jason M. ;

McGettigan, Suzanne ;

Kothari, Shawn ;

George, Sangeeth M. ;

Vonderheide, Robert H. ;

Amaravadi, Ravi K. ;

Karakousis, Giorgos C. . ;

Schuchter, Lynn M. ;

Xu, Xiaowei ;

Nathanson, Katherine L. ;

Wolchok, Jedd D. ;

Gangadhar, Tara C. ;

Wherry, E. John .

NATURE, 2017, 545 (7652) :60-+

[8]

Loi S, 2016, CANC RES S4, V76

[9] Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy [J].

Masuda, N. ;

Lee, S. -J. ;

Ohtani, S. ;

Im, Y. -H. ;

Lee, E. -S. ;

Yokota, I. ;

Kuroi, K. ;

Im, S. -A. ;

Park, B. -W. ;

Kim, S. -B. ;

Yanagita, Y. ;

Ohno, S. ;

Takao, S. ;

Aogi, K. ;

Iwata, H. ;

Jeong, J. ;

Kim, A. ;

Park, K. -H. ;

Sasano, H. ;

Ohashi, Y. ;

Toi, M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (22) :2147-2159

[10] The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014 [J].

Salgado, R. ;

Denkert, C. ;

Demaria, S. ;

Sirtaine, N. ;

Klauschen, F. ;

Pruneri, G. ;

Wienert, S. ;

Van den Eynden, G. ;

Baehner, F. L. ;

Penault-Llorca, F. ;

Perez, E. A. ;

Thompson, E. A. ;

Symmans, W. F. ;

Richardson, A. L. ;

Brock, J. ;

Criscitiello, C. ;

Bailey, H. ;

Ignatiadis, M. ;

Floris, G. ;

Sparano, J. ;

Kos, Z. ;

Nielsen, T. ;

Rimm, D. L. ;

Allison, K. H. ;

Reis-Filho, J. S. ;

Loibl, S. ;

Sotiriou, C. ;

Viale, G. ;

Badve, S. ;

Adams, S. ;

Willard-Gallo, K. ;

Loi, S. .

ANNALS OF ONCOLOGY, 2015, 26 (02) :259-271

← 1 2 →