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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
Author(s) -
Gluz Oleg,
KolbergLiedtke Cornelia,
Prat Aleix,
Christgen Matthias,
Gebauer Daniel,
Kates Ronald,
Paré Laia,
Grischke EvaMaria,
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
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32488
Subject(s) - triple negative breast cancer , medicine , breast cancer , gemcitabine , taxane , oncology , carboplatin , paclitaxel , cancer , chemotherapy , cisplatin
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 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.