Predictive gene expression profile for adjuvant taxane benefit in breast cancer in the MATADOR trial
Mark Opdam (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)
Annelot G.J. van Rossum (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)
Marlous Hoogstraat (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)
Gergana Bounova (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)
Hugo M. Horlings (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)
Erik van Werkhoven (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)
Ingrid A.M. Mandjes (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis)
A. Elise van Leeuwen – Stok (BOOG Study Center)
Lodewyk F.A. Wessels (Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis, TU Delft - Pattern Recognition and Bioinformatics, Oncode Institute)
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Abstract
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).
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