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Gluz, Oleg; Kolberg‐Liedtke, Cornelia; Prat, Aleix; Christgen, Matthias; Gebauer, Daniel; Kates, Ronald; Paré, Laia; Grischke, Eva‐Maria; Forstbauer, Helmut; Braun, Michael; Warm, Mathias; Hackmann, John; Uleer, Christoph; Aktas, Bahriye; Schumacher, Claudia; Kuemmel, Sherko; Wuerstlein, Rachel; Pelz, Enrico; Nitz, Ulrike; Kreipe, Hans Heinrich; Harbeck, Nadia

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

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  • Media type: E-Article
  • Title: 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
  • Contributor: Gluz, Oleg; Kolberg‐Liedtke, Cornelia; Prat, Aleix; Christgen, Matthias; Gebauer, Daniel; Kates, Ronald; Paré, Laia; Grischke, Eva‐Maria; Forstbauer, Helmut; Braun, Michael; Warm, Mathias; Hackmann, John; Uleer, Christoph; Aktas, Bahriye; Schumacher, Claudia; Kuemmel, Sherko; Wuerstlein, Rachel; Pelz, Enrico; Nitz, Ulrike; Kreipe, Hans Heinrich; Harbeck, Nadia
  • imprint: Wiley, 2020
  • Published in: International Journal of Cancer
  • Language: English
  • DOI: 10.1002/ijc.32488
  • ISSN: 0020-7136; 1097-0215
  • Keywords: Cancer Research ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:p>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 × nab‐pac 125 mg/m<jats:sup>2</jats:sup> (plus carbo AUC2 or gem 1,000 mg/m<jats:sup>2</jats:sup> 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% <jats:italic>vs</jats:italic>. 20%, <jats:italic>p</jats:italic> = 0.015), as was lower HER2 score (<jats:italic>p</jats:italic> &lt; 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all <jats:italic>p</jats:italic> &lt; 0.004), higher Ki‐67 (IHC; <jats:italic>p</jats:italic> &lt; 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 (<jats:italic>p</jats:italic> &lt; 0.05 for all). For nab‐pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: <jats:italic>p</jats:italic> = 0.05; FGFR4: <jats:italic>p</jats:italic> = 0.02; VEGFA: <jats:italic>p</jats:italic> = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event‐free survival: 92% <jats:italic>vs</jats:italic>. 71%, <jats:italic>p</jats:italic> &lt; 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.</jats:p>
  • Access State: Open Access