TY - JOUR
T1 - Predictive gene expression profile for adjuvant taxane benefit in breast cancer in the MATADOR trial
AU - Opdam, Mark
AU - van Rossum, Annelot G.J.
AU - Hoogstraat, Marlous
AU - Bounova, Gergana
AU - Horlings, Hugo M.
AU - van Werkhoven, Erik
AU - Mandjes, Ingrid A.M.
AU - van Leeuwen – Stok, A. Elise
AU - Canisius, Sander
AU - van Tinteren, Harm
AU - Imholz, Alex L.T.
AU - Portielje, Johanneke E.A.
AU - Bos, Monique E.M.M.
AU - Bakker, Sandra
AU - Wesseling, Jelle
AU - Kester, Lennart
AU - van Rheenen, Jacco
AU - Rutgers, Emiel J.
AU - de Menezes, Renee X.
AU - Wessels, Lodewyk F.A.
AU - Kok, Marleen
AU - Oosterkamp, Hendrika M.
AU - Linn, Sabine C.
AU - Soesan, Marcel
AU - Oosterkamp, Rianne M.
AU - Jeurissen, Frank
AU - Weijl, Nir
AU - Beelen, Karin J.
AU - van Bochove, Aart
AU - de Klerk, Gerty
AU - Vrijaldenhoven, Suzan
AU - van der Velden, Annette
AU - de Graaf, Hiltje
AU - Smeets, Marielle
AU - Terwogt, Jetske Meerum
AU - Schrama, Jolanda
AU - Kuijer, Philomeen
AU - Wilmink, Hanneke
AU - Hoekstra, Ronald
AU - Kroep, Judith
AU - Pruijt, Hans F.M.
AU - van Gerven, Leander
AU - Vos, Allert H.
AU - Erdkamp, Frans
AU - van Leeuwen-Breuk, Willemien G.
AU - de Graeff, Alexander
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/8/16
Y1 - 2024/8/16
N2 - 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).
AB - 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).
KW - Cancer
KW - Clinical genetics
KW - Oncology
UR - http://www.scopus.com/inward/record.url?scp=85201088378&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.110425
DO - 10.1016/j.isci.2024.110425
M3 - Article
AN - SCOPUS:85201088378
VL - 27
JO - iScience
JF - iScience
IS - 8
M1 - 110425
ER -