Franziska Würfel1, Ramona Erber2, Hanna Huebner1, Alexander Hein1, Michael P Lux1, Sebastian Jud1, Anita Kremer3, Hannah Kranich3, Andreas Mackensen3, Lothar Häberle1,4, Carolin C Hack1, Claudia Rauh1, Marius Wunderle1, Paul Gaß1, Shahrooz Rabizadeh5, Anna-Lisa Brandl1, Hanna Langemann1, Bernhard Volz1, Naiba Nabieva1, Rüdiger Schulz-Wendtland6, Diana Dudziak7, Matthias W Beckmann1, Arndt Hartmann2, Peter A Fasching1, Matthias Rübner1. 1. Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany. 2. Institute of Pathology, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany. 3. Department of Internal Medicine 5, Haematology and Oncology, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany. 4. Department of Gynecology and Obstetrics, Biostatistics Unit, Erlangen University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany. 5. NantOmics, LLC, Santa Cruz, CA, USA. 6. Institute of Diagnostic Radiology, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany. 7. Department of Dermatology, Laboratory of Dendritic Cell Biology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Abstract
BACKGROUND: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. METHODS: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. RESULTS: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). CONCLUSION: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.
BACKGROUND: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. METHODS: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. RESULTS: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). CONCLUSION: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.
Authors: A S Coates; E P Winer; A Goldhirsch; R D Gelber; M Gnant; M Piccart-Gebhart; B Thürlimann; H-J Senn Journal: Ann Oncol Date: 2015-05-04 Impact factor: 32.976
Authors: Matthias W Beckmann; Cosima Brucker; Volker Hanf; Claudia Rauh; Mayada R Bani; Stefanie Knob; Sabrina Petsch; Stefan Schick; Peter A Fasching; Arndt Hartmann; Michael P Lux; Lothar Häberle Journal: Onkologie Date: 2011-06-15
Authors: R Salgado; C Denkert; S Demaria; N Sirtaine; F Klauschen; G Pruneri; S Wienert; G Van den Eynden; F L Baehner; F Penault-Llorca; E A Perez; E A Thompson; W F Symmans; A L Richardson; J Brock; C Criscitiello; H Bailey; M Ignatiadis; G Floris; J Sparano; Z Kos; T Nielsen; D L Rimm; K H Allison; J S Reis-Filho; S Loibl; C Sotiriou; G Viale; S Badve; S Adams; K Willard-Gallo; S Loi Journal: Ann Oncol Date: 2014-09-11 Impact factor: 32.976
Authors: Carsten Denkert; Gunter von Minckwitz; Silvia Darb-Esfahani; Bianca Lederer; Barbara I Heppner; Karsten E 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 Journal: Lancet Oncol Date: 2017-12-07 Impact factor: 41.316
Authors: Peter A Fasching; Duan Liu; Steve Scully; Lothar Häberle; Richard M Weinshilboum; Liewei Wang; James N Ingle; Paulo C Lyra; Brigitte Rack; Alexander Hein; Arif B Ekici; Andre Reis; Andreas Schneeweiss; Hans Tesch; Tanja N Fehm; Georg Heinrich; Matthias W Beckmann; Matthias Ruebner; Hanna Huebner; Diether Lambrechts; Ebony Madden; Jess Shen; Jane Romm; Kim Doheny; Gregory D Jenkins; Erin E Carlson; Liang Li; Brooke L Fridley; Julie M Cunningham; Wolfgang Janni; Alvaro N A Monteiro; Daniel J Schaid Journal: Clin Cancer Res Date: 2022-08-02 Impact factor: 13.801
Authors: Florian Schütz; Peter A Fasching; Manfred Welslau; Andreas D Hartkopf; Achim Wöckel; Michael P Lux; Wolfgang Janni; Johannes Ettl; Diana Lüftner; Erik Belleville; Hans-Christian Kolberg; Friedrich Overkamp; Florin-Andrei Taran; Sara Y Brucker; Markus Wallwiener; Hans Tesch; Tanja N Fehm; Andreas Schneeweiss; Volkmar Müller Journal: Geburtshilfe Frauenheilkd Date: 2019-10-22 Impact factor: 2.915
Authors: Diana Lüftner; Florian Schütz; Elmar Stickeler; Peter A Fasching; Wolfgang Janni; Cornelia Kolberg-Liedtke; Hans-Christian Kolberg; Christoph Thomssen; Volkmar Müller; Tanja N Fehm; Erik Belleville; Simon Bader; Michael Untch; Manfred Welslau; Marc Thill; Hans Tesch; Nina Ditsch; Michael P Lux; Achim Wöckel; Bahriye Aktas; Andreas Schneeweiss; Rachel Würstlein; Andreas D Hartkopf Journal: Geburtshilfe Frauenheilkd Date: 2022-02-11 Impact factor: 2.915
Authors: Manfred Welslau; Volkmar Müller; Diana Lüftner; Florian Schütz; Elmar Stickeler; Peter A Fasching; Wolfgang Janni; Christoph Thomssen; Isabell Witzel; Tanja N Fehm; Erik Belleville; Simon Bader; Katharina Seitz; Michael Untch; Marc Thill; Hans Tesch; Nina Ditsch; Michael P Lux; Bahriye Aktas; Maggie Banys-Paluchowski; Andreas Schneeweiss; Nadia Harbeck; Rachel Würstlein; Andreas D Hartkopf; Achim Wöckel; Barbara Seliger; Chiara Massa; Hans-Christian Kolberg Journal: Geburtshilfe Frauenheilkd Date: 2022-06-03 Impact factor: 2.754
Authors: Paul Gass; Michael P Lux; Claudia Rauh; Alexander Hein; Mayada R Bani; Cornelia Fiessler; Arndt Hartmann; Lothar Häberle; Jutta Pretscher; Ramona Erber; David L Wachter; Rüdiger Schulz-Wendtland; Matthias W Beckmann; Peter A Fasching; Marius Wunderle Journal: BMC Cancer Date: 2018-10-29 Impact factor: 4.430
Authors: Franziska M Würfel; Ralph M Wirtz; Christoph Winterhalter; Mario Taffurelli; Donatella Santini; Anna Mandrioli; Elke Veltrup; Matthias Rübner; Peter A Fasching; Wolfgang Würfel; Claudio Zamagni Journal: Geburtshilfe Frauenheilkd Date: 2020-11-06 Impact factor: 2.915
Authors: Franziska M Wuerfel; Hanna Huebner; Lothar Häberle; Paul Gass; Alexander Hein; Sebastian M Jud; Carolin C Hack; Marius Wunderle; Rüdiger Schulz-Wendtland; Ramona Erber; Arndt Hartmann; Arif B Ekici; Matthias W Beckmann; Peter A Fasching; Matthias Ruebner Journal: Sci Rep Date: 2020-09-25 Impact factor: 4.379
Authors: Hannah Reimann; Andrew Nguyen; J Zachary Sanborn; Charles J Vaske; Stephen C Benz; Kayvan Niazi; Shahrooz Rabizadeh; Patricia Spilman; Andreas Mackensen; Matthias Ruebner; Alexander Hein; Matthias W Beckmann; Edith D van der Meijden; Judith Bausenwein; Sascha Kretschmann; Marieke Griffioen; Jeffrey Schlom; James L Gulley; Karin L Lee; Duane H Hamilton; Patrick Soon-Shiong; Peter A Fasching; Anita N Kremer Journal: J Immunother Cancer Date: 2021-06 Impact factor: 13.751