Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple-negative early breast cancer: Primary translational analysis of the WSG-ADAPT-TN trial

Gluz, Oleg; Kolberg-Liedtke, Cornelia; Prat, Aleix; Christgen, Matthias; Gebauer, Daniel; Kates, Ronald; Pare, Laia; Grischke, Eva-Maria; Forstbauer, Helmut; Braun, Michael; Warm, Mathias; Hackmann, John; Uleer, Christoph; Aktas, Bahriye; Schumacher, Claudia; Kuemmel, Sherko; Würstlein, Rachel; Pelz, Enrico; Nitz, Ulrike; Kreipe, Hans Heinrich und Harbeck, Nadia (2020): Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple-negative early breast cancer: Primary translational analysis of the WSG-ADAPT-TN trial. In: International Journal of Cancer, Bd. 146, Nr. 1: S. 262-271

Abstract

In the neoadjuvant WSG-ADAPT-TN trial, 12-week nab-paclitaxel + carboplatin (nab-pac/carbo) was highly effective and superior to nab-paclitaxel + gemcitabine (nab-pac/gem) in triple-negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients received 4 x nab-pac 125 mg/m(2) (plus carbo AUC2 or gem 1,000 mg/m(2) d1,8 q21). Expression of 119 genes and PAM50 scores by nCounter were available in 306/336 pretherapeutic samples. Interim survival analysis was planned after 36 months median follow-up. Basal-like (83.3%) compared to other subtypes was positively associated with pCR (38% vs. 20%, p = 0.015), as was lower HER2 score (p < 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all p < 0.004), higher Ki-67 (IHC;p < 0.001). For nab-pac/carbo, expression of immunological (CD8, PD1 and PFDL1) genes and proliferation markers (proliferation and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3 and TYMS) were positively associated with pCR (p < 0.05 for all). For nab-pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: p = 0.05;FGFR4: p = 0.02;VEGFA: p = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event-free survival: 92% vs. 71%, p < 0.001). In early TNBC, basal-like subtype, higher Ki-67 (IHC) and lower HER2 score were, associated with chemosensitivity. Chemoresistance pathways differed between the two taxane based combinations. Combination of proliferation/immune markers and PAM50 subtype could allow patient selection for further deescalated chemotherapy and/or immune treatment approaches.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0020-7136
• Sprache: Englisch