Journal ArticleDOI
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
Carsten Denkert,Gunter von Minckwitz,Jan C. Brase,Bruno Valentin Sinn,Stephan Gade,Ralf Kronenwett,Berit M. Pfitzner,Christoph Salat,Sherene Loi,Sherene Loi,Wolfgang D. Schmitt,Christian Schem,Karin Fisch,Silvia Darb-Esfahani,Keyur Mehta,Christos Sotiriou,Stephan Wienert,Peter Klare,Fabrice Andre,Frederick Klauschen,Jens-Uwe Blohmer,Kristin Krappmann,Marcus Schmidt,Hans Tesch,Sherko Kümmel,Peter Sinn,Christian Jackisch,Manfred Dietel,Toralf Reimer,Michael Untch,Sibylle Loibl +30 more
TLDR
Investigating the immunogenicity of human epidermal growth factor receptor 2 -positive and triple-negative breast cancers and immunologically relevant genes in the neoadjuvant GeparSixto trial found immunologic factors were highly significant predictors of therapy response in the trial, particularly in patients treated with Cb.Abstract:
Purpose Modulation of immunologic interactions in cancer tissue is a promising therapeutic strategy. To investigate the immunogenicity of human epidermal growth factor receptor 2 (HER2) –positive and triple-negative (TN) breast cancers (BCs), we evaluated tumor-infiltrating lymphocytes (TILs) and immunologically relevant genes in the neoadjuvant GeparSixto trial. Patients and Methods GeparSixto investigated the effect of adding carboplatin (Cb) to an anthracycline-plus-taxane combination (PM) on pathologic complete response (pCR). A total of 580 tumors were evaluated before random assignment for stromal TILs and lymphocyte-predominant BC (LPBC). mRNA expression of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) as well as immunosuppressive factors (IDO1, PD-1, PD-L1, CTLA4, FOXP3) was measured in 481 tumors. Results Increased levels of stromal TILs predicted pCR in univariable (P < .001) and multivariable analyses (P < .001). pCR rate was 59.9% in LPBC and 33.8% for non-LPBC (P < .001). pC...read more
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Andreas D. Hartkopf,Florin-Andrei Taran,Markus Wallwiener,Christina B. Walter,Bernhard K. Krämer,Eva-Maria Grischke,Sara Y. Brucker +6 more
TL;DR: This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer.
Journal ArticleDOI
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease
TL;DR: The most relevant molecular findings in TNBC from the past decade are discussed and the most promising therapeutic opportunities derived from these data are discussed.
Journal ArticleDOI
Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015
Alan S. Coates,Eric P. Winer,A. Goldhirsch,Richard D. Gelber,Michael Gnant,Martine Piccart-Gebhart,Beat Thürlimann,H.-J. Senn +7 more
TL;DR: The 14th St Gallen International Breast Cancer Conference (2015) reviewed new evidence on locoregional and systemic therapies for early breast cancer and summarizes treatment-oriented classification of subgroups and treatment recommendations.
Journal ArticleDOI
The immune contexture in cancer prognosis and treatment
Wolf H. Fridman,Laurence Zitvogel,Catherine Sautès-Fridman,Catherine Sautès-Fridman,Catherine Sautès-Fridman,Guido Kroemer +5 more
TL;DR: The immune contexture, which is determined by the density, composition, functional state and organization of the leukocyte infiltrate of the tumour, can yield information that is relevant to prognosis, prediction of a treatment response and various other pharmacodynamic parameters.
Journal ArticleDOI
Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy
Carsten Denkert,Gunter von Minckwitz,Silvia Darb-Esfahani,Bianca Lederer,Barbara Ingold Heppner,Karsten Weber,Jan Budczies,Jens Huober,Frederick Klauschen,Jenny Furlanetto,Wolfgang D. Schmitt,Jens-Uwe Blohmer,Thomas Karn,Berit M. Pfitzner,Sherko Kümmel,Knut Engels,Andreas Schneeweiss,Arndt Hartmann,Aurelia Noske,Peter A. Fasching,Christian Jackisch,Marion van Mackelenbergh,Peter Sinn,Christian Schem,Claus Hanusch,Michael Untch,Sibylle Loibl +26 more
TL;DR: The hypothesis that breast cancer is immunogenic and might be targetable by immune-modulating therapies is supported and increased TIL concentration predicted response to neoadjuvant chemotherapy in all molecular subtypes assessed.
References
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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Journal ArticleDOI
Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer
Julie R. Brahmer,Scott S. Tykodi,Scott S. Tykodi,Laura Q.M. Chow,Wen-Jen Hwu,Suzanne L. Topalian,Patrick Hwu,Charles G. Drake,Luis H. Camacho,John S. Kauh,Kunle Odunsi,Henry C. Pitot,Omid Hamid,Shailender Bhatia,Renato G. Martins,Keith D. Eaton,Shuming Chen,Theresa M. Salay,Suresh Alaparthy,Joseph F. Grosso,Alan J. Korman,Susan M. Parker,Shruti Agrawal,Stacie M. Goldberg,Drew M. Pardoll,Ashok Kumar Gupta,Jon M. Wigginton +26 more
TL;DR: Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
Journal ArticleDOI
Nivolumab plus Ipilimumab in Advanced Melanoma
Jedd D. Wolchok,Harriet Kluger,Margaret K. Callahan,Michael A. Postow,Naiyer A. Rizvi,Alexander M. Lesokhin,Neil H. Segal,Charlotte E. Ariyan,Ruth-Ann Gordon,Kathleen Reed,Matthew M. Burke,Anne Caldwell,Stephanie Anne Kronenberg,Blessing Agunwamba,Xiaoling Zhang,Israel Lowy,Hector David Inzunza,William Feely,Christine Horak,Quan Hong,Alan J. Korman,Jon M. Wigginton,Ashok Kumar Gupta,Mario Sznol +23 more
TL;DR: Conurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients.
Journal ArticleDOI
Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis
Patricia Cortazar,Lijun Zhang,Michael Untch,Keyur Mehta,Joseph P. Costantino,Norman Wolmark,Hervé Bonnefoi,David Cameron,Luca Gianni,Pinuccia Valagussa,Sandra M. Swain,Tatiana M. Prowell,Sibylle Loibl,D. Lawrence Wickerham,Jan Bogaerts,José Baselga,Charles M. Perou,Gideon M. Blumenthal,Jens Uwe Blohmer,Eleftherios P. Mamounas,Jonas Bergh,Vladimir Semiglazov,Robert Justice,Holger Eidtmann,Soonmyung Paik,Martine Piccart,Rajeshwari Sridhara,Peter A. Fasching,Leen Slaets,Shenghui Tang,Bernd Gerber,Charles E. Geyer,Richard Pazdur,Nina Ditsch,Priya Rastogi,Wolfgang Eiermann,Gunter von Minckwitz +36 more
TL;DR: In this paper, the authors compared the three most commonly used definitions of pathological complete response (ypT0 ypN0, ypT0/is ypNs0, and ypTsN0/IsYPN0) for their association with EFS and overall survival in clinical trials of neoadjuvant treatment of breast cancer.
Journal ArticleDOI
The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014
Roberto Salgado,Carsten Denkert,Sandra Demaria,Nicolas Sirtaine,Frederick Klauschen,Giancarlo Pruneri,Stephan Wienert,G. Van den Eynden,Frederick L. Baehner,Frédérique Penault-Llorca,E. A. Perez,E. A. Thompson,William Fraser Symmans,Andrea L. Richardson,Jane E. Brock,Carmen Criscitiello,Helen Bailey,Michail Ignatiadis,Giuseppe Floris,Joseph A. Sparano,Zuzana Kos,Torsten O. Nielsen,David L. Rimm,Kimberly H. Allison,Jorge S. Reis-Filho,Sibylle Loibl,Christos Sotiriou,Giuseppe Viale,Sunil S. Badve,Sylvia Adams,Karen Willard-Gallo,Sherene Loi +31 more
TL;DR: Current data on the clinical validity and utility of TILs in BC are reviewed in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections.
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The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014
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