iScience (Aug 2024)
Predictive gene expression profile for adjuvant taxane benefit in breast cancer in the MATADOR trial
- Mark Opdam,
- Annelot G.J. van Rossum,
- Marlous Hoogstraat,
- Gergana Bounova,
- Hugo M. Horlings,
- Erik van Werkhoven,
- Ingrid A.M. Mandjes,
- A. Elise van Leeuwen – Stok,
- Sander Canisius,
- Harm van Tinteren,
- Alex L.T. Imholz,
- Johanneke E.A. Portielje,
- Monique E.M.M. Bos,
- Sandra Bakker,
- Jelle Wesseling,
- Lennart Kester,
- Jacco van Rheenen,
- Emiel J. Rutgers,
- Renee X. de Menezes,
- Lodewyk F.A. Wessels,
- Marleen Kok,
- Hendrika M. Oosterkamp,
- Sabine C. Linn,
- Sabine C. Linn,
- Marcel Soesan,
- Rianne M. Oosterkamp,
- Frank Jeurissen,
- Nir Weijl,
- Alex L.T. Imholz,
- Johanneke E.A. Portielje,
- Karin J. Beelen,
- Monique E.M.M. Bos,
- Aart van Bochove,
- Gerty de Klerk,
- Suzan Vrijaldenhoven,
- Annette van der Velden,
- Hiltje de Graaf,
- Marielle Smeets,
- Jetske Meerum Terwogt,
- Jolanda Schrama,
- Philomeen Kuijer,
- Hanneke Wilmink,
- Ronald Hoekstra,
- Judith Kroep,
- Hans F.M. Pruijt,
- Leander van Gerven,
- Allert H. Vos,
- Frans Erdkamp,
- Willemien G. van Leeuwen-Breuk,
- Alexander de Graeff
Affiliations
- Mark Opdam
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Annelot G.J. van Rossum
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Marlous Hoogstraat
- Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Gergana Bounova
- Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Hugo M. Horlings
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Erik van Werkhoven
- Biometrics department, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Ingrid A.M. Mandjes
- Data center, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- A. Elise van Leeuwen – Stok
- Dutch Breast Cancer Research Group, BOOG Study Center, Amsterdam, the Netherlands
- Sander Canisius
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Harm van Tinteren
- Biometrics department, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Alex L.T. Imholz
- Department of Medical Oncology, Deventer Ziekenhuis, Deventer, the Netherlands
- Johanneke E.A. Portielje
- Department of Medical Oncology, HagaZiekenhuis, The Hague, the Netherlands; Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands
- Monique E.M.M. Bos
- Department of Internal Oncology, Reinier de Graaf Gasthuis, Delft, the Netherlands
- Sandra Bakker
- Department of Medical Oncology, Zaans Medisch Centrum, Zaandam, the Netherlands
- Jelle Wesseling
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
- Lennart Kester
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Jacco van Rheenen
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Emiel J. Rutgers
- Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Renee X. de Menezes
- Biostatistics Centre, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Lodewyk F.A. Wessels
- Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, Delft, the Netherlands
- Marleen Kok
- Division of Tumor biology & Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
- Hendrika M. Oosterkamp
- Department of Medical Oncology, Haaglanden Medisch Centrum, The Hague, the Netherlands
- Sabine C. Linn
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pathology, University Medical Center, Utrecht, the Netherlands; Corresponding author
- Sabine C. Linn
- Marcel Soesan
- Rianne M. Oosterkamp
- Frank Jeurissen
- Nir Weijl
- Alex L.T. Imholz
- Johanneke E.A. Portielje
- Karin J. Beelen
- Monique E.M.M. Bos
- Aart van Bochove
- Gerty de Klerk
- Suzan Vrijaldenhoven
- Annette van der Velden
- Hiltje de Graaf
- Marielle Smeets
- Jetske Meerum Terwogt
- Jolanda Schrama
- Philomeen Kuijer
- Hanneke Wilmink
- Ronald Hoekstra
- Judith Kroep
- Hans F.M. Pruijt
- Leander van Gerven
- Allert H. Vos
- Frans Erdkamp
- Willemien G. van Leeuwen-Breuk
- Alexander de Graeff
- Journal volume & issue
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Vol. 27,
no. 8
p. 110425
Abstract
Summary: The primary objective of the prospective, randomized, multicenter, phase 3 biomarker Microarray Analysis in breast cancer to Taylor Adjuvant Drugs Or Regimens trial (MATADOR: ISRCTN61893718) is to generate a gene expression profile that can predict benefit from either docetaxel, doxorubicin, and cyclophosphamide (TAC) or dose-dense scheduled doxorubicin and cyclophosphamide (ddAC). Patients with a pT1-3, pN0-3 tumor were randomized 1:1 between ddAC and TAC. The primary endpoint was a gene profile-treatment interaction for recurrence-free survival (RFS). We observed 117 RFS events in 664 patients with a median follow-up of 7 years. Hallmark gene set analyses showed significant association between enrichment in immune-related gene expression and favorable outcome after TAC in hormone receptor-negative, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) (triple-negative breast cancer [TNBC]). We validated this association in TNBC patients treated with TAC on H&E slides; stromal tumor-infiltrating lymphocytes (sTILs) ≥20% was associated with longer RFS (hazard ratio 0.18, p = 0.01), while in patients treated with ddAC no difference in RFS was seen (hazard ratio 0.92, p = 0.86, pinteraction = 0.02).
